Implantable vascular device

ABSTRACT

An valve prosthesis, such as an artificial venous valve, having a support frame and leaf structure comprising one or more leaflets in which the outer edge of each leaflet engages the inner circumference of the bodily passageway along a serpentine path urged against the passageway by an expandable frame, while the inner edges move in response to fluid to restrict retrograde flow. Optionally, one or more elements can extend from the support frame/leaf structure to provide centering support and/or protection from the leaflet adhering to the vessel wall. In one embodiment, the centering support structure comprises a second or third expandable frames attached to and extending from the proximal and/or distal ends of main valve structure and support frame. In another embodiment, one or more support elements extend outward from the valve support frame to engage the vessel wall to provide greater longitudinal stability.

RELATED APPLICATIONS

This application claims priority to provisional application Ser. No.60/403,783, filed Aug. 15, 2002 and is a continuation-in-part ofapplication Ser. No. 09/777,091, filed Feb. 5, 2001 now U.S. Pat. No.7,452,371. This application is related to currently pending U.S.application Ser. No. 10/642,513, entitled “Stent and Method of Forming aStent with Integral Barbs”, of Pavcnik, et al., filed concurrently Aug.15, 2003, which is incorporated by reference herein.

TECHNICAL FIELD

This invention relates to medical devices, more particularly, tointraluminal devices.

BACKGROUND OF THE INVENTION

As minimally invasive techniques and instruments for placement ofintraluminal devices have developed over recent years, the number andtypes of treatment devices have proliferated as well. Stents, stentgrafts, occlusion devices, artificial valves, shunts, etc., haveprovided successful treatment for a number of conditions that heretoforerequired surgery or lacked an adequate solution altogether. Minimallyinvasive intravascular devices especially have become popular with theintroduction of coronary stents to the U.S. market in the early 1990s.Coronary and peripheral stents have been proven to provide a superiormeans of maintaining vessel patency. In addition, they have subsequentlybeen used as filter, occluders, or in conjunction with grafts as arepair for abdominal aortic aneurysm, with fibers or other materials asocclusion devices, and as an intraluminal support for artificial valves,among other uses.

Some of the chief goals in designing stents and related devices includeproviding sufficient radial strength to supply sufficient force to thevessel and prevent device migration. An additional concern in peripheraluse, is having a stent that is resistant to external compression.Self-expanding stents are superior in this regard to balloon expandablestents which are more popular for coronary use. The challenge isdesigning a device that can be delivered intraluminally to the target,while still being capable of adequate expansion. Self-expanding stentsusually require larger struts than balloon expandable stents, thusincreasing their profile. When used with fabric or other coverings thatrequire being folded for placement into a delivery catheter, the problemis compounded.

There exists a need to have a basic stent, including a fabric orbiomaterial covering, that is capable of being delivered with a lowprofile, while still having a sufficient expansion ratio to permitimplantation in larger vessels, if desired, while being stable,self-centering, and capable of conforming to the shape of the vessel.There is a further need to have a intraluminal valve that can bedeployed in vessels to replace or augment incompetent native valves,such as in the lower extremity venous system to treat patients withvenous valve insufficiency. Such a valve should closely simulate thenormal functioning valve and be capable of permanent implantation withexcellent biocompatibility.

SUMMARY OF THE INVENTION

The foregoing problems are solved and a technical advance is achieved inan illustrative implantable valve that is deployed within a bodilypassage, such as a blood vessel or the heart, to regulate or augment thenormal flow of blood or other bodily fluids. The valve includes acovering having oppositely facing curvilinear-shaped surfaces (upper andlower) against which fluid traveling in a first or second directionwithin the bodily passage exerts force to at least partially open orclose the valve. At least one outer edge of the covering resilientlyengages and exerts force against the wall of the vessel and has arcuateshape that provides at least a partial seal against the wall.

In one aspect of the invention, the covering comprises a plurality ofleaflets, each leaflet having a body extending from a wall-engagingouter edge to a free edge which is cooperable with one or more opposingleaflets to prevent flow in one direction, such as retrograde flow,while at least a portion of the leaflets having sufficient flexibility,when in situ to move apart, thereby creating a valve orifice thatpermits flow in the opposite direction, such as normal blood flow. Theouter edge of each leaflet is adapted to engage and resilient exertforce against a wall of the bodily passage such that it extends in botha longitudinal and circumferential directions along the vessel wall toat least partially seal a portion of the vessel lumen, while the freeedge of each leaflet traverses the passageway across the diameter of thevessel.

In another aspect of the invention, the valve includes a frame that iscovered by a piece of biocompatible material, preferably anExtracellular Collagen Matrix (ECM) such as small intestinal submucosa(SIS) or another type of submucosal-derived tissue. Other potentialbiomaterials include allographs such as harvested native valve tissue.The material is slit or otherwise provided with an opening along oneaxis to form two triangular valve leaflets over a four-sided frame. Inthe deployed configuration, the leaflets are forced open by normal bloodflow and subsequently close together in the presence of backflow to helpeliminate reflux. Other configurations include a two-leaflet valvehaving an oval or elliptically shaped frame, and valves having three ormore legs and associated leaflets, which provide a better distributionof the load exerted by the column of fluid acting on the leaflets.

In still another aspect of the invention, the valve portion of thedevice, which preferably, but not essentially, includes a saddle-shaped,two-leaflet valve having a serpentine-shaped frame with the resilientouter edges of the leaflets that are sealable about entire circumferenceof the vessel (as depicted in FIG. 25), further includes additionalcentering support structure to help align the device within the vesselto prevent tilting that can compromise the performance of the valve. Thecentering support structure can be separate components attached to thevalve portion frame, or be integrally formed with the valve portionframe (e.g., cut from the same piece of cannula).

A first series of embodiments include centering support structure thatextends from the proximal end, distal end, or both ends of the valveportion. This includes, a second (or third) frame, an expandable stent,helical coil, an elongate projection or strut, an inflatable member,extended portion cut from the same cannula used to form the valveportion, or other structure that can be deployed ahead of the valveportion to provide longitudinal support, or remain within the deliverysystem during deployment of the valve portion, wherein the centeringsupport structure is then also deployed. As with any of the embodiments,the prosthesis support frame, including centering support structure, canbe formed from since piece of metal cannula (e.g., nitinol) or someother suitable biocompatible material by laser cutting, etching, or someother well-known method.

A second series of embodiments include centering support structure, suchas a plurality of lateral elements or arms and/or supplemental legs,that extends laterally from the valve portion to provide additionalcontact points along the circumference of the vessel for longitudinalsupport, contact points being generally defined as the bends whichtypically supply concentrated radial force against the vessel wall (asopposed to the struts that although in contact the vessel wall,typically supply less radial force). Additionally, the lateral elements,which are preferably positioned behind the leaflets and interposedbetween the leaflet and vessel wall, can offer protection to theleaflets so that they are at least partially blocked and generallyunable to adhere to the vessel wall, which can collapse onto theleaflets due to how the valve radially expands and conforms to thevessel. The lateral elements or arms can comprise separate componentsattached to the basic valve portion frame, or the frame itself cancomprise multiple elements or subassemblies that can be assembled toform a closed valve portion frame with two laterally extending arms.Each lateral arm can include one contact point or additional contactpoints for added stability.

In another embodiment, the centering support structure comprises twolateral arms, which protect the two leaflets and provide longitudinalsupport, and two supplemental legs about the distal end of the valveportion for further stabilization to prevent tilting. One method offorming the frame includes attaching two zig-zag or serpentine-shapedstents end to end, with struts, sutures, or another well-knownmechanism. Each zig-zag stent comprises a four or more serpentinesections with at least two opposite sections comprising either lateralarms (proximal stent) or supplemental legs (distal stent), with theother two serpentine sections on each stent comprising a half of one ofthe valve section legs. Strut lengths, wire diameters, eye diameters,and angles and widths of serpentine sections can be varied to produceoptimum radial pressure that the device exerts on the vessel wall,depending on the size of the valve and vessel diameter. The optimalradial pressure is one at which the valve conforms to the vessel andprevents reflux without causing erosion or damage to the vessel wallthat could lead to rupture.

In the double serpentine stent embodiment, the covering comprising theleaflets is attached to the frame so that each leaflet spans the twostents or serpentine row section with a lateral arm extending outward sothat it is external to the leaflet and frame. In an embodiment in whichthe serpentine stents are attached using a long strut that also addsrigidity to the valve legs which helps prevent partial collapse due tothe weight of the blood column, the ends of the struts extend beyond thebends of the valve portion frame to serve as barbs. To help prevententanglement with the barbs during loading of the device with thedelivery system, and modifying radial pressure, the adjacent lateralarms and supplemental legs can be made shorter or longer than theadjacent serpentine sections that comprise the valve legs, so that theirrespective contact points are offset relative to the ends of the barbs.Additionally, the struts of the serpentine sections can be curved toproduce a more rounded configuration for improved conformity with thevessel. The frame can also be laser cut or otherwise formed from nitinoltubing, or some other material, to create multiple serpentine rowsections (e.g., at least 2-4) interconnected by struts with the leafletsspanning multiple rows.

In another embodiment of the present invention, the valve portion isattached inside an expandable stent, or a sleeve of material, such asSIS, that is configured to provide longitudinal stability and preventtilting. The sleeve can further include an anchoring stent about one endthat is deployed ahead of, or after, the valve portion to preventtilting of the valve.

In still another aspect of the present invention, the frame of thedevice is modified by placing one or more of the bends under tensionwhich results in the frame assuming a second shape that has superiorcharacteristics of placement within the vessel. One method of adjustingthe shape includes forming the bends in the wire at an initial angle,e.g., 150°, that is larger than the desired final angle, e.g., 90° for afour-sided valve, so when the frame is constrained into the finalconfiguration, the sides are arcuate and bow outward slightly. Thecurvature of the sides allows the sides to better conform to the roundedcontours of the vessel wall when the valve is deployed. In deviceshaving a full or partial covering of material over the frame, a secondmethod of modifying the shape is to use the material to constrain theframe in one axis. One such embodiment includes a four-sided valve withtwo triangular-shaped halves of material, such as SIS, where thematerial constrains the frame in a diamond shape. This puts the bend ofthe frame under stress or tension which permits better positioningwithin the vessel. It also allows the diagonal axis of the frame withthe slit or orifice to be adjusted to the optimal length to properlysize the frame for the vessel such that the leaflets open to allowsufficient flow, but do not open to such a degree that they contact thevessel wall. The potential benefits of both adding tension to the bendsto bow the sides and constraining the frame into a diamond shape usingthe covering, can be combined in a single embodiment or employedseparately.

In still another aspect of the present invention, the device includes aframe that in one embodiment, is formed from a single piece of wire orother material having a plurality of sides and bends eachinterconnecting adjacent sides. The bends can be coils, fillets, orother configurations to reduce stress and improve fatigue properties.The single piece of wire is preferably joined by an attachmentmechanism, such as a piece of cannula and solder, to form a closedcircumference frame. The device has a first configuration wherein thesides and bends generally lie within a single, flat plane. In anembodiment having four equal sides, the frame is folded into a secondconfiguration where opposite bends are brought in closer proximity toone another toward one end of the device, while the other opposite endsare folded in closer proximity together toward the opposite end of thedevice. In the second configuration, the device becomes a self-expandingstent. In a third configuration, the device is compressed into adelivery device, such as a catheter, such that the sides are generallybeside one another. While the preferred embodiment is four-sided, otherpolygonal shapes can be used as well. The frame can either be formedinto a generally flat configuration, or into the serpentineconfiguration for deployment from a single or multiple sections of wireor other material. Besides rounded wire, the frame can comprise wires ofother cross-sectional shapes (e.g., oval, delta, D-shape), or flat wire.Additionally, the frame can be molded from a polymer or compositematerial, or formed from a bioabsorbable material such as polyglycolicacid and materials with similar properties. Another method is to lasercut the frame out of a metal tube, such as stainless steel or nitinol.Still yet another method is to spot weld together, or otherwise attach,a series of separate struts that become the sides of a closed frame. Infurther alternative embodiments, the frame can be left with one or moreopen gaps that are bridged by the material stretched over the remainderof the frame. The frame can also be formed integrally with the covering,typically as a thickened or strengthened edge portion that gives thedevice sufficient rigidity to allow it to assume the deployedconfiguration in the vessel. To prevent the frame from radiallyexpanding within the vessel beyond the point which would be consideredsafe or desirable, the device can be formed into the serpentineconfiguration and a circumferentially constraining mechanism (orcircumferential member), such as a tether, strut, sleeve, etc., placedaround the device, or built into the frame, to expand or unfold duringdeployment of the device to limit its expansion to a given diameter,such as that which is slightly larger than the vessel into which it isplaced to allow anchoring, but not permit the device to exert to great aforce on the vessel wall.

In another aspect of the present invention, one or more barbs can beattached to the frame for anchoring the device in the lumen of a vessel.The barbs can be extensions of the single piece of wire or othermaterial comprising the frame, or they can represent a second piece ofmaterial that is separately attached to the frame by a separateattachment mechanism. An elongated barb can be used to connectadditional devices with the second and subsequent frames attached to thebarb in a similar manner. Additional barbs can be secured to the devicefrom cannulae placed over the frame. In embodiments in which the frameis formed as a single piece, such as when cut from a sheet of materialor injection molded, the barbs can be formed as integral extensions ofthe frame.

In still another aspect of the present invention, a covering, which canbe a flexible synthetic material such as DACRON, or expandedpolytetrafluorethylene (ePTFE), or a natural or collagen-based material,such as an allographic tissue (such as valvular material) or axenographic implant (such as SIS), can be attached to the device withsutures or other means to partially, completely, or selectively restrictfluid flow. When the covering extends over the entire aperture of theframe, the frame formed into the second configuration functions as anvascular occlusion device that once deployed, is capable of almostimmediately occluding an artery. An artificial valve, such as that usedin the lower legs and feet to correct incompetent veins, can be made bycovering half of the frame aperture with a triangular piece of material.The artificial valve traps retrograde blood flow and seals the lumen,while normal blood flow is permitted to travel through the device. Inrelated embodiments, the device can be used to form a stent graft forrepairing damaged or diseased vessels. In a first stent graftembodiment, a pair of covered frames or stent adaptors are used tosecure a tubular graft prosthesis at either end and seal the vessel.Each stent adaptor has an opening through which the graft prosthesis isplaced and an elongated barb is attached to both frames. In anotherstent graft embodiment, one or more frames in the second configurationare used inside a sleeve to secure the device to a vessel wall.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a top view of one exemplary embodiment of the presentinvention;

FIG. 1A depicts a magnified view of the area circled in FIG. 1.

FIG. 2 depicts a pictorial view of the embodiment of FIG. 1;

FIG. 3 depicts a top view and enlarged, partial cross-sectional views ofa second exemplary embodiment of the present invention;

FIG. 3A depicts a magnified view of area 3A circled in FIG. 3.

FIG. 3B depicts a magnified view of area 3B circled in FIG. 3.

FIG. 4 depicts a side view of the embodiment of FIG. 3 deployed in avessel;

FIG. 5 depicts a enlarged partial view of the embodiment of FIG. 1;

FIG. 6 depicts a partially-sectioned side view of the embodiment of FIG.1 inside a delivery system;

FIG. 7 depicts a top view of a third embodiment of the presentinvention;

FIG. 8 depicts a side view of the embodiment of FIG. 7 deployed in avessel;

FIGS. 9-11 depict enlarged partial views of other embodiments of thepresent invention;

FIG. 12 depicts a top view of a fourth embodiment of the presentinvention;

FIGS. 13-14 depicts side views of the embodiment of FIG. 12;

FIG. 15 depicts a top view of a fifth embodiment of the presentinvention;

FIG. 16 depicts a side view of the embodiment of FIG. 15;

FIG. 17 depicts a side view of a sixth embodiment of the presentinvention;

FIG. 18 depicts an enlarged pictorial view of a seventh embodiment ofthe present invention;

FIG. 19 depicts a top view of an eighth embodiment of the presentinvention;

FIG. 20 depicts a top view of a first embodiment of a multi-leafletintraluminal valve of the present invention;

FIG. 21 depicts a top view of a second embodiment of a multi-leafletintraluminal valve;

FIG. 21A depicts a partial top view of another embodiment of leaflets ofthe present invention;

FIG. 21B depicts a top view of another embodiment of leaflet of thepresent invention;

FIGS. 22-23 depict side views of the embodiment of FIG. 21 when deployedin a vessel;

FIGS. 24-25 depict pictorial views of the embodiments of FIG. 21 whendeployed in a vessel;

FIGS. 26-26A depict the method of attaching the covering to theembodiment of FIG. 21;

FIG. 27 depicts a pictorial view of the basic valve of FIG. 21 upondeployment with an alternative leaflet embodiment;

FIGS. 28-31 depict top views of selected embodiments of the presentinvention, made using the method shown in FIG. 28;

FIG. 32 depicts a pictorial view of an embodiment of a stent graft thatincludes stent adaptors of the present invention;

FIG. 33 depicts a delivery system for deploying an embodiment of thepresent invention; and

FIG. 34 depicts a pictorial view of the present invention havingreturned to the first configuration following formation into the secondconfiguration;

FIGS. 35-36 depict top views of a three-leg valve embodiment of thepresent invention, before and after being constrained;

FIG. 37 depicts a pictorial view of the embodiment of FIG. 35 in thedeployed configuration;

FIGS. 38-39 depict top views of four-leg valve embodiments of thepresent invention, before and after being constrained;

FIG. 40 depicts a pictorial view of the embodiment of FIG. 38 in thedeployed configuration;

FIG. 41 depicts a top view of a frame formed from a sheet of material;

FIG. 41A depicts a detail view of the embodiment of FIG. 41;

FIG. 42 depicts a top view of a third embodiment of an intraluminalvalve;

FIG. 43 depicts a pictorial view a frame embodiment formed into adeployed configuration;

FIG. 44 depicts atop view of an embodiment of implantable valve havingan integrally formed frame and covering;

FIG. 45 depicts a cross-sectional view taken along line 45-45 of FIG.44;

FIG. 46 depicts a cross-sectional view of a second embodiment of valvehaving an integrally formed frame and covering;

FIG. 47 depicts a top view of an intraluminal valve embodiment having anopen frame;

FIGS. 48-49 depict a pictorial views of an intraluminal valveembodiments that includes a circumferentially constraining mechanism;

FIG. 50 depicts a top view of the embodiment of FIG. 22;

FIG. 51 depicts the embodiment of FIG. 22 having titled followingdeployment within a vessel;

FIG. 52 depicts a top view of the valve in FIG. 51;

FIGS. 53-57 depict pictorial views of embodiments of the presentinvention that include centering support structure comprising one ormore adjoining frames or stents;

FIG. 58 depicts a side view of an embodiments of the present inventionthat includes centering support structure comprising a pair of lateralarms;

FIGS. 59-61 depict pictorial views of different frame embodiments of thebasic embodiment of FIG. 58;

FIGS. 62-62A depict pictorial views of embodiments of the presentinvention that include lateral support arms and supplemental supportlegs;

FIGS. 63-64 depict pictorial views of embodiments of the presentinvention wherein the frame and centering support structure comprise aserpentine stent frame;

FIG. 65 depict a pictorial view of an embodiment of the presentinvention having two lateral support arms originating from each leg;

FIGS. 66-67 depict pictorial views of embodiments of the presentinvention wherein the valve and centering support structure are formedfrom a cannula;

FIG. 68 depicts a side view of an embodiment of the present inventionwherein the centering support structure comprises an expandable stentexternal to the valve portion;

FIG. 69 depicts a top view of an embodiment of the present inventionwherein the valve and centering support structure are formed from a flatsheet of material;

FIG. 70 depicts a pictorial view of the embodiment of FIG. 69;

FIG. 71 depicts a pictorial view of an embodiment of the presentinvention wherein the centering support structure includes a helicalconfiguration;

FIG. 72 depicts a pictorial view of an embodiment of the presentinvention wherein the centering support structure includes an adjoiningzig-zag stent;

FIGS. 73-74 depict pictorial and side views of an embodiment of thepresent invention wherein the centering support structure includes adistal projection;

FIG. 75 depicts a side view of an embodiment of the present inventionwherein the valve and adjoining stent are interconnected by a sleeve ofmaterial;

FIGS. 76-79 depict tops view of embodiments of the present inventionwherein the flat square frame is formed from multiple components;

FIG. 80 depicts a side view an alternative frame embodiment of the basicvalve of FIGS. 62-62A;

FIG. 81 depicts a flattened, view of a stent component of the embodimentof FIG. 80;

FIG. 82 depicts an alternate embodiment of the stent component of FIG.81;

FIG. 83 depicts a side view of an embodiment similar to that of FIG. xformed out of a cannula;

FIG. 84 depicts a side view of an embodiment similar to that of FIG. xformed out of a cannula;

FIGS. 85-86 depict side views of valve embodiments in which the leafletsspan multiple serpentine row sections of the prosthesis support frame.

DETAILED DESCRIPTION

The invention is further illustrated by the following (preceding)pictorial embodiments, which in no way should be construed as furtherlimiting. The present invention specifically contemplates otherembodiments not illustrated but intended to be included in the appendedclaims. FIGS. 1-11, 18-19 are directed to a basic stent frame; FIGS.12-14 are directed to a single-leaflet valve; FIGS. 15-16 are directedto an occluder (or filter); FIGS. 17 and 32 are directed to a stentadaptor for a stent graft, FIG. 20-27, 35-40, 42-50 are directed to amulti-leaf valve; and FIGS. 28-31 are directed to a constrained framewhich can be used to form any of the other embodiments.

FIG. 1 depicts a top view of one embodiment of the medical device 10 ofthe present invention comprising a frame 11 of resilient material,preferably metal wire made of stainless steel or a superelastic alloy(e.g., nitinol). While round wire is depicted in each of the embodimentsshown herein, other types, e.g., flat, square, triangular, D-shaped,delta-shaped, etc. may be used to form the frame. In the illustrativeembodiment, the frame comprises a closed circumference 62 of a singlepiece 59 of material that is formed into a device 10 having a pluralityof sides 13 interconnected by a series of bends 12. The depictedembodiment includes four sides 13 of approximately equal length.Alternative embodiments include forming a frame into any polygonalshape, for example a pentagon, hexagon, octagon, etc. One alternativeembodiment is shown in FIG. 19 that includes a four-sided frame 11having the general shape of a kite with two adjacent longer sides 66 andtwo adjacent shorter sides 67. In the embodiment of FIG. 1, the bends 12interconnecting the sides 13 comprise a coil 14 of approximately one anda quarter turns. The coil bend produces superior bending fatiguecharacteristics than that of a simple bend 40, as shown in FIG. 9, whenthe frame is formed from stainless steel and most other standardmaterials. The embodiment of FIG. 9 may be more appropriate, however, ifthe frame is formed from nitinol (NiTi) or other superelastic alloys, asforming certain type of bends, such as coil 14, may actually decreasefatigue life of a device of superelastic materials. Therefore, the bend12 should be of a structure that minimizes bending fatigue. Alternativebend 12 embodiments include an outward-projecting fillet 41 as shown inFIG. 10, and an inward-projecting fillet 42 comprising a series ofcurves 63, as shown in FIG. 11. Fillets are well known in the stent artas a means to reduce stresses in bends. By having the fillet extendinward as depicted in FIG. 11, there is less potential trauma to thevessel wall.

When using stainless steel wire, the size of the wire which should beselected depends on the size of device and the application. An occlusiondevice, for example, preferably uses 0.010″ wire for a 10 mm squareframe, while 0.014″ and 0.016″ wire would be used for 20 mm and 30 mmframes, respectively. Wire that is too stiff can damage the vessel, notconform well to the vessel wall, and increase the profile of the devicewhen loaded in the delivery system prior to deployment.

Returning to FIG. 1, the single piece 59 of material comprising theframe 11 is formed into the closed circumference 62 by securing thefirst and second ends 60, 61 with an attachment mechanism 15 such as apiece of metal cannula. The ends 60, 61 of the single piece 59 are theninserted into the cannula 15 and secured with solder 25, a weld,adhesive, or crimping to form the closed frame 11. The ends 60, 61 ofthe single piece 59 can be joined directly without addition of a cannula15, such as by soldering, welding, or other methods to join ends 61 and62. Besides joining the wire, the frame could be fabricated as a singlepiece of material 59, by stamping or cutting the frame 11 from anothersheet (e.g., with a laser), fabricating from a mold, or some similarmethod of producing a unitary frame.

A alternate method of forming the frame 11 of the present invention isdepicted in FIGS. 76-79, whereby rather than one continuous length ofwire being used, the frame 11 comprises a two or more sub-portions 205that include an attachment 15 such as a weld, solder, glue, crimpingwith the illustrative cannula 15, or another means, or combinationthereof, to form a closed circumference 62. In the embodiment depictedin FIGS. 76-77, a first and a second C-shaped sub-portion 206, 207 areoverlaid such that first ends 210 of the C-shaped sub-portion 206, 207extend beyond the adjoining sub-portion to form a barb 16 for anchoringthe device 10 within the vessel. As shown in FIG. 77, the assembledframe 11 includes four barbs that either represent the ends 210, 211 ofthe sub-portions 206, 207, or are formed by cutting away excess material228 from the ends, depending on how the sides 13 of the C-shapedportions are sized.

FIGS. 78-79 depict an alternative embodiment using sub-portions 205 toassemble a closed frame, whereby there are four L-shaped sub-portions214, 220, 221, 222 with attachments at each of the four sides 13 thatmake up the closed circumference 62. In the illustrative embodimentsonly two of the ends 217 are used to form barbs 17, 18; however,additional barbs can be formed by lengthening any leg of the L-shapedsub-portion 214, 220, 221, 222 such that it extends beyond the closedcircumference 62. Other configurations are possible in addition to thosedepicted, for example, having three sub-portions 205 or even more thanfour if making a frame having more than four sides.

The device 10 depicted in FIG. 1 is shown in its first configuration 35whereby all four bends 20, 21, 22, 23 and each of the sides 13 generallylie within a single flat plane. To resiliently reshape the device 10into a second configuration 36, shown in FIG. 2, the frame 11 of FIG. 1is folded twice, first along one diagonal axis 94 with opposite bends 20and 21 being brought into closer proximity, followed by opposite bends22 and 23 being folded together and brought into closer proximity in theopposite direction. The second configuration 36, depicted in FIG. 2, hastwo opposite bends 20, 21 oriented at the first end 68 of the device 10,while the other opposite bends 22, 23 are oriented at the second end 69of the device 10 and rotated approximately 90° with respect to bends 20and 21 when viewed in cross-section. The medical device in the secondconfiguration 36 can be used as a stent 44 to maintain an open lumen 34in a vessel 33, such as a vein, artery, or duct. The bending stressesintroduced to the frame 11 by the first and second folds required toform the device 10 into the second configuration 36, apply forceradially outward against the vessel wall 70 to hold the device 10 inplace and prevent vessel closure. Absent any significant plasticdeformation occurring during folding and deployment, the device in thesecond configuration 36, when not with the vessel or other constrainingmeans, will at least partially return to the first configuration 25,although some deformation can occur as depicted in FIG. 34, depending onthe material used. It is possible to plastically form the stent intothis configuration which represents an intermediate condition betweenthe first configuration (which it also can obtain) and the secondconfiguration. It is also possible to plastically deform the device 10into the second configuration 36, such that it does not unfold whenrestraint is removed. This might be particularly desired if the deviceis made from nitinol or a superelastic alloy.

The standard method of deploying the medical device 10 in a vessel 33,depicted in FIG. 6, involves resiliently forming the frame 11 into athird configuration 37 to load into a delivery device 26, such as acatheter. In the third configuration 37 the adjacent sides 13 aregenerally beside each other in close proximity extending generally alongthe same axis. To advance and deploy the device from the distal end 28of the delivery catheter 26, a pusher 27 is placed into the catheterlumen 29. When the device 10 is fully deployed, it assumes the secondconfiguration 36 within the vessel as depicted in FIG. 2. The sides 13of the frame, being made of resilient material, conform to the shape ofthe vessel wall 70 such that when viewed on end, the device 10 has acircular appearance when deployed in a round vessel. As a result, sides13 are arcuate or slightly bowed out to better conform to the vesselwall.

A second embodiment of the present invention is depicted in FIG. 3wherein one or more barbs 16 are included to anchor the device 10following deployment. As understood, a barb can be a wire, hook, or anystructure attached to the frame and so configured as to be able toanchor the device 10 within a lumen. The illustrative embodimentincludes a first barb 16 with up to three other barbs 17, 71, 72,indicated in dashed lines, representing alternative embodiments. Asdepicted in detail view A of FIG. 3, the barb combination 38 thatcomprises barbs 17 and 18, each barb is an extension of the single piece59 of material of the frame 11 beyond the closed circumference 59. Theattachment cannula 15 secures and closes the single piece 59 of materialinto the frame 11 as previously described, while the first and secondends 60, 61 thereof, extend from the cannula 15, running generallyparallel with the side 13 of the frame 11 from which they extend, eachpreferably terminating around or slightly beyond respective bends 20,23. To facilitate anchoring, the distal end 19 of the barb 16 in theillustrative embodiment contains a bend or hook.

Optionally, the tip of the distal end 19 can be ground to a sharpenedpoint for better tissue penetration. To add a third and fourth barb asshown, a double ended barb 39 comprising barbs 71 and 72 is attached tothe opposite side 13 as defined by bends 21 and 22. Unlike barbcombination 38, the double barb 39, as shown in detail view B of FIG. 3,comprises a piece of wire, usually the length of barb combination 38,that is separate from the single piece 59 comprising the main frame 11.It is secured to the frame by attachment mechanism 15 using the methodsdescribed for FIG. 1. FIG. 4 depicts barb 17 (and 18) engaging thevessel wall 70 while the device 10 is in the second, deployedconfiguration 36. While this embodiment describes up to a four barbsystem, more than four can be used.

FIG. 7 depicts a top view of a third embodiment of the present inventionin the first configuration 35 that includes a plurality of frames 11attached in series. In the illustrative embodiment, a first frame 30 andsecond frame 31 are attached by a barb 16 that is secured to each frameby their respective attachment mechanisms 15. The barb 16 can be adouble-ended barb 39 as shown in FIG. 3 (and detail view B) that isseparate from the single pieces 59 comprising frames 30 and 31, or thebarb may represent a long extended end of the one of the single pieces59 as shown in detail view A of FIG. 3. Further frames, such as thirdframe 32 shown in dashed lines, can be added by merely extending thelength of the barb 16. FIG. 8 depicts a side view of the embodiment ofFIG. 7 in the second configuration 36 as deployed in a vessel 33.

FIGS. 12-18 depict embodiments of the present invention in which acovering 45 comprising a sheet of fabric, collagen (such as smallintestinal submucosa), or other flexible material is attached to theframe 11 by means of sutures 50, adhesive, heat sealing, “weaving”together, crosslinking, or other known means. FIG. 12 depicts a top viewof a fourth embodiment of the present invention while in the firstconfiguration 35, in which the covering 45 is a partial covering 58,triangular in shape, that extends over approximately half of theaperture 56 of the frame 11. When formed into the second configuration36 as shown in FIGS. 13-14, the device 10 can act as an artificial valve43 such as the type used to correct valvular incompetence. FIG. 13depicts the valve 43 in the open configuration 48. In this state, thepartial covering 58 has been displaced toward the vessel wall 70 due topositive fluid pressure or flow in a first direction 46, e.g., normalvenous blood flow, thereby opening a passageway 65 through the frame 11and the lumen 34 of the vessel 33. As the muscles relax, producing flowin a second, opposite direction 47, e.g., retrograde blood flow 47, asshown in FIG. 14, the partial covering 58 acts as a normal valve bycatching the backward flowing blood and closing the lumen 34 of thevessel. In the case of the artificial valve 43, the partial covering 58is forced against the vessel wall to seal off the passageway 65, unlikea normal venous valve which has two leaflets, which are forced togetherduring retrograde flow. Both the artificial valve 43 of the illustrativeembodiment and the normal venous valve, have a curved structure or cuspthat facilitates the capture of the blood and subsequent closure. Inaddition to the triangular covering, other possible configurations ofthe partial covering 58 that result in the cupping or trapping of fluidin one direction can be used. Selecting the correct size of valve forthe vessel ensures that the partial covering 58 properly seals againstthe vessel wall 70. If the lumen 34 of the vessel is too large for thedevice 10, there will be retrograde leakage around the partial covering58.

FIG. 15 depicts a top view of a fifth embodiment of the presentinvention in the first configuration 35, whereby there is a fullcovering 57 that generally covers the entire aperture 56 of the frame11. When the device 10 is formed into the second configuration 36, asdepicted in FIG. 16, it becomes useful as an occlusion device 51 toocclude a duct or vessel, close a shunt, repair a defect, or otherapplication where complete or substantially complete prevention of flowis desired. As an intravascular device, studies in swine have shownocclusion to occur almost immediately when deployed in an artery or theaorta with autopsy specimens showing that thrombus and fibrin which hadfilled the space around the device. The design of the present inventionpermits it to be used successfully in large vessels such as the aorta.Generally, the occlusion device should have side 13 lengths that are atleast around 50% or larger than the vessel diameter in which they are tobe implanted.

FIGS. 17-18 depict two embodiments of the present invention in which thedevice 10 functions as a stent graft 75 to repair a damaged or diseasedvessel, such as due to formation of an aneurysm. FIG. 17 shows a stentgraft 75 having a tubular graft prosthesis 54 that is held in place by apair of frames 11 that function as stent adaptors 52, 53. Each stentadaptor 52, 53 has a covering attached to each of the frame sides 13which includes a central opening 55 through which the graft prosthesis54 is placed and held in place by friction or attachment to preventmigration. One method of preventing migration is placement of a stentadaptor 52, 53 according to the present invention at each end andsuturing the graft prosthesis 54 to the covering of the stent adaptors52, 53. The stent adaptors 52, 53 provide a means to seal blood flowwhile centering the graft prosthesis in the vessel. A long double-endedbarb 39 connects to each stent adaptor 52, 53 and assists to furtheranchor the stent graft 75. In the embodiment depicted in FIG. 18, thecovering 45 comprises a outer sleeve 64 that is held in place by firstand second 30, 31 frames that function as stents 44 to hold and seal thesleeve 64 against a vessel wall and maintain an open passageway 65. Inthe illustrative embodiment, the stents 44 are secured to the graftsleeve 64 by sutures 50 that are optionally anchored to the coils 14 ofthe bends 12. If the embodiment of FIG. 18 is used in smaller vessels, asingle frame 11 can be used at each end of the stent graft 75. Anotherstent graft 75 embodiment is depicted in FIG. 32 for repairing a vesseldefect 97, such as an aneurysm in a bifurcated vessel. The stent adaptor52 of the present invention is placed in the common vessel 96 such asthe abdominal aorta. Two tubular grafts 54 are secured within anaperture 55 in the covering 45 of the frame 11 by one or more internalstent adapters 102, or another type of self-expanding stent, that biasthe opening of the grafts 54 against the surrounding covering 45 toprovide an adequate seal. Each leg 98, 99 of the stent graft prosthesis75 transverses the vessel defect 97 and feeds into their respectivevessel branches 100, 101 such the right and left common iliac arteries.As with the embodiment of FIG. 17, a second stent adapter 53 can be usedto anchor the other end of the tubular graft 54 in each vessel branch100, 101.

FIGS. 20-27 and 35-41 depict embodiments of present inventions in whichthe device 10 comprises an implantable valve having multiple leaflets 25that act together to regulate and augment the flow of fluid through aduct or vessel 33, or within the heart to treat patients with damaged ordiseased heart valves. The covering 45 of each of these embodimentsincludes one or a series of partial coverings 58 that form the leaflets25 of the valve. As with the other embodiments, the covering 45 maycomprise a biomaterial or a synthetic material. While DACRON, expandedpolytetrafluoroethylene (ePTFE), or other synthetic biocompatiblematerials can be used to fabricate the covering 45, a naturallyoccurring biomaterial, such as collagen, is highly desirable,particularly a specially derived collagen material known as anextracellular matrix (ECM), such as small intestinal submucosa (SIS).Besides SIS, examples of ECM's include pericardium, stomach submucosa,liver basement membrane, urinary bladder submucosa, tissue mucosa, anddura mater. SIS is particularly useful, and can be made in the fashiondescribed in Badylak et al., U.S. Pat. No. 4,902,508; IntestinalCollagen Layer described in U.S. Pat. No. 5,733,337 to Carr and in 17Nature Biotechnology 1083 (November 1999); Cook et al., WIPO PublicationWO 98/22158, dated 28 May 1998, which is the published application ofPCT/US97/14855. Irrespective of the origin of the valve material(synthetic versus naturally occurring), the valve material can be madethicker by making multilaminate constructs, for example SIS constructsas described in U.S. Pat. Nos. 5,968,096; 5,955,110; 5,885,619; and5,711, 969. Animal data show that the SIS used in venous valves of thepresent invention can be replaced by native tissue in as little as amonth's time. In addition to xenogenic biomaterials, such as SIS,autologous tissue can be harvested as well, for use in forming theleaflets of the valve. Additionally Elastin or Elastin Like Polypetides(ELPs) and the like offer potential as a material to fabricate thecovering or frame to form a device with exceptional biocompatibility.Another alternative would be to used allographs such as harvested nativevalve tissue. Such tissue is commercially available in a cryopreservedstate.

To more completely discuss and understand the multi-leaflet valve 43embodiments of FIGS. 20-27, 35-41, it is useful to now add certainsupplemental terminology which in some instances, could be applied tothe embodiments depicted in the earlier figures. In the illustrativemulti-leaflet embodiments, the valve 43 is divided into a plurality oflegs 113, each of which further comprises a leaflet 25. To anchor,support, and provide the proper orientation of the leaflets 25, aseparate or integral frame 11 is included, such as the wire frame 11depicted in FIG. 1. Ideally, the wire used to construct the frame ismade of a resilient material such as 302, 304 stainless steel; however,a wide variety of other metals, polymers, or other materials arepossible. It is possible for the frame to be made of the same materialas the leaflets 25. One other example of a suitable frame material wouldbe a superelastic alloy such as nitinol (NiTi). Resiliency of the frame11, which provides radial expandability to the valve 43 when in thesecond configuration 36 for deployment, is not necessarily an essentialproperty of the frame. For example, optional barbs 16 can provide themeans to anchor the valve 43 after delivery, even if the valve 43 lackssufficient expansile force to anchor itself against the vessel wall.Additionally, the frame can comprise a ductile material with the device10 being designed to be balloon expandable within the vessel.

Typically, when used as a valve to correct venous insufficiency in thelower extremities, the valve 43 in situ comprises a plurality of bends12 of the frame, that provide the majority of the outward radial forcethat helps anchor the device to vessel wall 70, as depicted in FIGS.22-27. When deployed, the frame assumes the undulating or serpentineconfiguration characteristic of the invention with a first series ofbends 115 of the first or proximal end alternating with a second seriesof bends 116 of the second or distal end, with the second or distalbends 116 being located at the bottom of the valve distal to the heartand the first or proximal bends 115 being located at the top of thevalve proximal to the heart. It should be understood that the valve canassume other orientations, depending on the particular clinical use, andthus, any directional labels used herein (‘distal’, ‘top’, etc.) aremerely for reference purposes. The leaflet 25, which generally coversthe valve leg 113 and therefore, assumes the same roughly triangular ‘U’or ‘V’ shape of that portion of the frame 11 perimeter, includes anresilient arcuate outer edge 112 that conforms to and/or seals with thecontours of the vessel wall 70, and an inner edge 111 that traverses thevessel lumen 34. The central portion or body 156 of the leaflet 25extends inward from the vessel wall 70 and outer edge 112 in an obliquedirection toward the first end 68 of the valve 43 where it terminates atthe inner edge 111 thereof. The valve leaflets that come in contact withthe vessel wall carry the supporting frame along the outer edge tobetter conform to and directly seal with the vessel wall. The leaflets25 assume a curvilinear shape when in the deployed configuration 36. Theportion of the body 156 proximate the inner edge 111 is sufficientlyflexible such that is can move in and out of contact with the inner edge111 the opposite or other leaflets 25; however, the remainder of thebody 156, particular that near the outer edge 112 or second end 69 ofthe device 10, can be made less flexible or even rigid in someinstances, essentially functioning more for support, similar to thefunction of the frame 11, rather than to cooperate with other leaflet(s)25. FIGS. 20-27 depict the present invention as an implantable,intraluminal, vascular adapted for use as a implantable multi-leafletvalve 43 including a stent 44 or frame 11 with at least a partialcovering 58. The covering comprises a first and a second valve leaflets78, 79 that at least partially seal the aperture 56 within the frame 11while the valve 43 is in the deployed configuration 36 and forms theopening 117 or valve orifice which regulates the flow of fluid 46, 47through the valve. FIG. 20 shows the device 10 in the first, generallyplanar configuration 35 where the frame 11 is generally rectangular orin particular square in shape. The partial covering 58 forming theleaflets 78, 79 generally extends across the entire frame 11 with theaperture 56 comprising a slit 108 that extends across the first axis 94of the frame 11, the first axis being defined as traversing diagonallyopposite bends (22 and 23 in this example) that are in line with thevalve orifice 117 that forms the valve 43. The covering 45 is thereforedivided into at least first and second portions (making it a partialcovering 58) which define the first and second valve leaflets 78, 79. Toform the leaflets 78, 79, a complete covering 45 can be slit open alongthe axis after it is affixed to the frame, or at least first and secondadjacent triangular portions (partial coverings 58) can be separatelyattached, eliminating the need for mechanically forming a slit 108. Inthe embodiment of FIG. 20, the slit 108 is made in the covering 45 suchthat the slit terminates a few millimeters from each of the corner bends22, 23, creating a pair of corner gaps 155, thereby eliminating two ofthe most likely sources of leakage around the valve 43. In theillustrative embodiments, the outer edge 112 of the partial covering 58that comprises the leaflet 25 is stretched over the frame 11 comprisingthe valve leg 113 and sutured or otherwise attached as disclosed herein.The leaflet 25 is secured in place such that the material is fairlytaut, such that when the valve 43 is situated in the vessel 33 and itsdiameter constrained to slightly less than the valve width 146, theleaflet 25 assumes a relatively loose configuration that gives it theability to flex and invert its shape, depending on the direction offluid flow. The inner edge 111 of the leaflet 25 is generally free andunattached to the frame and generally extends between the bends 22 and23 (the bends 115 of the first end) of the valve leg 113. The inner edge111 may be reinforced by some means, such as additional material or thinwire, that still would allow it to be sufficiently pliable to be able toseal against another leaflet 25 when retrograde flow 47 forces theleaflets 78, 79 together. The leaflet 25 is sized and shaped such thatthe inner edge 111 of one leaflet 78 can meet or overlap with the inneredge 111 of the opposing leaflet 79 (or leaflets, e.g., 119, 120),except when degree of normal, positive flow 46 is sufficient to forcethe leaflets 25 open to permit fluid passage therethrough.

The embodiments of FIGS. 21-27 are configured into an elongated diamondshape 153 in the planar configuration 35 with the distance between thetwo bends 22, 23 aligned with the valve orifice 117 and first axis 94being less than the distance between bends 20 and 21 along the second,perpendicular axis 95. This diamond configuration 153 can beaccomplished by forming the frame 11 into that particular shape, orconstraining a square frame into a diamond shape 153, which will bediscussed later. By configuring the valve 43 into the diamond shape 153,the valve legs 127, 128 become more elongated in shape, which can helpadd stability when positioning the device 10 during deployment, providesmore surface area to receive retrograde flow, and more closely mimics anatural venous valve. In the deployed configuration 36 of the embodimentof FIG. 21, which is shown in FIGS. 22-25, the valve leaflets 78, 79 areforced apart by the normal pulsatile blood flow 46 (FIGS. 22, 24). Therespective valve leaflets 78, 79 naturally move back into closerproximity following the pulse of blood. Retrograde blood flow 47 forcesthe valve leaflets 78, 79 against one another, as depicted in FIGS. 23and 25 thereby closing off the lumen 34 of the vessel 33 and the valveorifice 117.

FIGS. 21A-21B depict embodiments of the valve 43 in which each leaflet78, 79 includes a flap 77 of overhanging material along the slit edge111 to provide advantageous sealing dynamics when the valve 43 is in thedeployed configuration 36 as depicted in FIGS. 22-25. The flaps 77 aretypically formed by suturing two separate pieces of covering 45 materialto the frame such that the inner edge 111 is extendable over the slit108 and inner edge 111 of the adjacent leaflet 25. By overlapping withan adjacent flap 77 or leaflet 25, the flap 77 can provide additionalmeans to help seal the valve orifice 117. Two embodiments of leaflets 25with flaps 77 are shown. In FIG. 21A, the inner edge 111 is basicallystraight and extends over the first axis 94 of the frame 11. The flaps77 can be cut to create a corner gap 155 that covers and seals thecorner region around the bend 22, 23. In the embodiment of FIG. 21B, theflap 77 is cut such that there is a notch 157 in the leaflet where theleaflet meets the corner bends 22, 23. While these flaps 77 may providebenefit in certain embodiments, the optional flaps 77 shown in FIG. 21are not necessary to provide a good seal against backflow 47 if thevalve 43 and leaflets 25 are properly sized and configured.

FIGS. 26-26A depict one method of affixing a covering 45 comprising abiomaterial, such as SIS, to the frame 11 which has been constrainedusing a temporary constraining mechanism 121, such as a suture, toachieve the desired frame configuration. As shown in FIG. 26, thecovering 45 is cut larger than the frame 11 such that there is anoverhang 80 of material therearound, e.g., 5-10 mm. The frame 11 iscentered over the covering 45 and the overhang 80 is then folded overfrom one long side 142, with the other long side 143 subsequently beingfolded over the first. As shown in FIG. 26A, the covering 45 is suturedto the frame along one side 142, typically using forceps 158 and needle,thereby enclosing the frame 11 and the coiled eyelet 14 with theoverhang 80 along side 142. The covering 45 is sutured to the frame withresorbable or non-resorbable sutures 50 or some other suitable method ofattaching two layers of biomaterials can be used. In the case of SIS, asingle ply sheet, usually about 0.1 mm thick, is used in the hydratedcondition. In the illustrative embodiments, 7-0 Prolene suture is used,forming a knot at one bend (e.g., bend 20), then continuing to the nextbend (e.g., 22) with a running suture 50, penetrating the layers of SISaround the frame at about 1-2 mm intervals with loops formed to hold thesuture 50 in place. When the next coil turn 14 is reached, several knotsare formed therethrough, and the running suture 50 continues to the nextcoil turn 14. If barbs are present, such as shown in the embodiment ofFIG. 21, the suture 50 is kept inside of the barbs 16 located about eachcoil turn 14. In the illustrative example, the covering 45 is affixed tothe frame 11 such that one side of the overhang 80 is not sutured overthe other side in order to maintain the free edge of the overhang 80,although the alternative condition would be an acceptable embodiment.Alternative attachment methods include, but are not limited to, use of abiological adhesive, a cross-linking agent, heat welding, crimping, andpressure welding. For synthetic coverings, other similar methods ofjoining or attaching materials are available which are known in themedical arts. The covering 45, whether made from a biomaterial orsynthetic material, can be altered in ways that improve its function,for example, by applying a coating of pharmacologically active materialssuch as heparin or cytokines, providing a thin external cellular layer,e.g., endothelial cells, or adding a hydrophilic material or othertreatment to change the surface properties.

Once the covering 45 has been sutured into place or otherwise attachedto the frame, the overhang 80 is folded back away from the frame, asshown on the second side 143 of the frame of FIG. 26A, and part of theexcess overhang 80 is trimmed away with a scalpel 159 or other cuttinginstrument to leave a 2-4 mm skirt around the frame 11. The overhang 80or skirt provides a free edge of SIS (or material with similarremodeling properties) to help encourage more rapid cell in growth fromthe vessel wall, such that the SIS replaces native tissue as quickly aspossible. An unattached edge of the overhang 80 can also form a cornerflap 81 or pocket as depicted in FIG. 27. This corner flap 81 can serveto catch retrograde blood flow 47 to provide a better seal between thedevice 10 and the vessel wall 70 as well as providing an improvedsubstrate for ingrowth of native intimal tissue from the vessel 33, ifmade of SIS or another material with remodeling properties.

Referring now to FIGS. 28-31, the frame 11 used to form the valve 43embodiments, e.g., FIGS. 20-27, that are placed in the legs or otherdeep veins as replacement for incompetent venous valves, is sizedaccording to the size of the target vessel. For example, a typicalvenous valve might be made of 0.0075″ 304 stainless steel mandril wirewith an attachment mechanism 15 comprising 23 to 24 gauge thin-wallstainless steel cannula or other tubing. Larger wire (e.g., 0.01″) andattachment cannula 15 are typically used for valves 43 of the largerdiameter (greater than 15 mm). Selection of the attachment cannula 15depends on competing factors. For example, use of larger gaugeattachment cannula 15 results in a slightly increased device 10 profile,yet it includes additional room for flux when the attachment mechanism15 is soldered over the continuous wire 59 comprising the frame 11. FIG.30 best depicts an uncovered frame 11 used to form a venous valve 43,wherein the length of the sides 13 typically range from about 15 to 25mm. For larger frames, heavier gauge wire is typically used. Forexample, 25 mm frames might use 0.01″ wire, with larger diameterembodiments such as stent occluders used for femoral bypass or stentadaptors, such as shown in FIGS. 17 and 32, requiring an even heaviergauge. The appropriate gauge or thickness of the frame wire also dependson the type of alloy or material used. As previously disclosed, theframe is typically formed in a generally flat configuration and thenmanipulated into its characteristic serpentine configuration and loadedinto a delivery system. Therefore, the frame usually will tend toreassume the first or generally flat configuration if the restraint ofthe delivery system or vessel is removed. Deformation of the frame 11can occur after it has been manipulated into the second configuration,however, such that it no longer will lie completely flat, as depicted inFIG. 34. This angle of deformation 129, which varies depending on theframe thickness and material used, generally does not compromise thefunction of the device 10, which can be reconfigured into the serpentineconfiguration (of the second, deployed configurations) without loss offunction.

The frame 11 of the present invention can be made either by forming aseries of bends in a length of straight wire and attaching the wire toitself, as previously discussed, to form a closed configuration, or theframe 11 can be formed in the deployment (second) configuration 35 asdepicted in FIGS. 41-41A by cutting it out of a flat sheet 152 ofmaterial, e.g., stainless steel or nitinol. Further finishing procedurescan then be performed after it has been cut or formed, such aspolishing, eliminating sharp edges, adding surface treatments orcoatings, etc. In addition to metal, the frame 11 can comprise one ormore polymers, composite materials, or other non-metallic materials suchas collagen with the frame either being cut from a thin sheet of thematerial, or molded into the deployment configuration 36 as depicted inFIG. 43. Unlike the majority of the depicted embodiments, the frame 11of FIG. 43 does not naturally assume a flattened configuration 35 whenthe device 10 is unconstrained by the vessel or delivery system.

The illustrative embodiments of FIGS. 41-41A and 43 include integralbarbs 124 that extend from the frame 11, which being formed as a closedframe, does not have free ends 60, 61 that can be used to serve as barbs16 as depicted in FIG. 3 and other embodiments. FIGS. 41-41A depict aseries of integral barbs 124 comprising V-shaped cuts 139 transversingthe thickness of the flat metal frame 11, which are bent outward to formthe barb 16. In the embodiment of FIG. 43, the integral barbs 124 areformed along with the frame 11 with two extending from the frame ateither side of each bend 12. These integral barbs 124 can be designedinto the mold if the frame 11 is formed out of a polymer material. Thenumber, arrangement, and configuration of the integral barbs 124 isgenerally not critical and can vary according to design preference andthe clinical use of the device. The barbs 16 may or may not penetratethe covering, depending on their design and other factors, including thethickness and type of covering used.

While the frame embodiment of FIG. 43 can be formed from a variety ofmedical grade polymers having properties that permit the frame tofunction as a supporting structure for the valve leaflets 78, 79, itshould be noted that for some uses, it may be desirable to form theframe 11 from a material that can be degraded and adsorbed by the bodyover time to advantageously eliminate a frame structure can would remainin the vessel as a foreign body and that could possibly fracture and/orcause perforation of the vessel wall. A number of bioabsorbablehomopolymers, copolymers, or blends of bioabsorbable polymers are knownin the medical arts. These include, but are not necessarily limited to,poly-alpha hydroxy acids such as polyactic acid, polylactide,polyglycolic acid, or polyglycolide; trimethlyene carbonate;polycaprolactone; poly-beta hydroxy acids such as polyhydroxybutyrate orpolyhydroxyvalerate; or other polymers such as polyphosphazines,polyorganophosphazines, polyanhydrides, polyesteramides,polyorthoesters, polyethylene oxide, polyester-ethers (e.g.,polydioxanone) or polyamino acids (e.g., poly-L-glutamic acid orpoly-L-lysine). There are also a number of naturally derivedbioabsorbable polymers that may be suitable, including modifiedpolysaccharides such as cellulose, chitin, and dextran or modifiedproteins such as fibrin and casein.

FIGS. 44-46 depicts two exemplary embodiments in which the frame 11 isintegral with the covering 45. In the embodiment of FIG. 44, the valve43 is formed as a single piece of material, such as a flexible polymericor collagen-based material, whereby there is a thin, compliant centralportion comprising the covering 45 or leaflets 78, 79, and a thickenededge 141 portion that comprises the frame 11. The valve 43, shown in thegenerally flat configuration 35, can be also formed into the deploymentconfiguration 36 (see FIG. 43). Optionally, the material of the frame 11portion can be subjected to treatments or processes that add rigidity orother desired characteristics that permit the frame to better supportthe covering 45 portion or anchor the device 10 to the vessel wall. Aswith the embodiment of FIG. 43, optional intergral barbs 124 can beincluded along the frame 11. In addition to forming a thickened edge 141to serve as the frame 11, other layers of different materials can belaminated to or blended with the edge portion to provide the desiredproperties. As another alternative to the thickened edge 141 portion ofFIGS. 44-45, the outside edge 112 of the covering 45 can be folded overitself to form a rolled edge 140 (FIG. 46) that adds rigidity to serveas a frame 11. The rolled edge 140 can be held in placed with a glue,resin, or similar bonding agent 144. For example, the covering 45 androlled edge 140 can comprise a sheet of SIS with a bonding agent 144such as collagen glue or other bioabsorbable material used to secure therolled portion and after hardening, to add the necessary degree ofrigidity for the valve 43 (or occluder, filter, stent adaptor, etc.) toassume the deployment configuration within the vessel. Excess of thebonding agent 144 can be fashioned to structural elements that can serveto help anchor the device 10 within the vessel. It is also within thescope of the invention to eliminate a discernable frame 11 by changingthe material or material properties along the outer edge 112 of theleaflets, by adding or incorporating one or more different material oragents along the outer edge 112 of covering 45 such that the stiffnessand/or resiliency increased, thereby allowing the frame to hold adesired shape during deployment, while still allowing the adjacentcovering material to be sufficiently flexible to function as a leaflet25. If the illustrative valve 43 lacks the radial expandability toanchor itself to the vessel wall, it may be mounted on a balloon toexpand the valve 43 and anchor the barbs, if present, into the vesselwall.

The illustrative embodiments of the present invention generally includea closed frame 11 to give the device 10 its form. FIG. 47 depicts anexample in which the frame 11 portion is not a closed structure. Rather,a portion of the covering 45 used to span a gap 145 in the frame suchthat a portion of the outside edge 112 (of leaflet 79 in this example)is unsupported therealong. The length of the gaps 145 and theirdistribution can vary as long as the frame 11 is still able to fulfillits role to support and define the shape of the valve 43 or device 10.

FIGS. 21-31 depict various embodiments in which the bends 20, 21, 22, 23are placed in a resiliently tensioned or stressed state after beinginitially formed such that the bends were not under tension. The term‘tension’, as used herein, is meant to describe generally a forcedapplied to a resilient material or structure against the naturaltendency of the material or structure, whether or not the force is infact tensile, compression, or torsional. Further incremental forcesapplied will generally encounter greater resistance than would otherwisebe exhibited by the material or structure, such as a compression spring,which exerts a force (resilience) resisting compression proportional tothe distance the spring has already been compressed. The addition oftension to one or more bends 12 of the device frame 11 can alter theproperties of the frame 11 and result in improved sealingcharacteristics or the ability of the device 10 to impinge upon thevessel wall 70 to prevent migration or shifting. In the illustrativeembodiments, the coil turn 14 is formed as previously disclosed wherebyeach bend 12 is in a untensioned state with the adjacent sides 13 havingan initial angle after formation of the bend 12. For example, in theembodiment of FIG. 20, the initial angle 109 after the bends are formedand the final angle 110 after the frame 11 is assembled are bothapproximately 90°. Therefore, the bends 12 of the embodiment of FIG. 20are not placed under any significant degree of tension. In theembodiments of FIGS. 21-31, the frame is restrained to permanently placethe bends 12 under tension such that the angle between the sides 122,123 adjacent to the bend 12 is increased or decreased by some method ofmanipulation to produce a resiliently tensioned bend 118 (FIGS. 26 and29) having a final angle 110 different than the initial angle 109 (e.g.,FIG. 28).

Referring particularly to FIGS. 21-28, the covering 45 (including a fullor a partial covering 58) can be attached to the frame 11 of the valve43 or other embodiment of the present invention, to constrain agenerally untensioned square frame 11 (such as in FIG. 1) andsubsequently form an altered shape 82, such as a diamond 153, in whichthe distance between bends 20 and 21 is lengthened and the distancebetween bends 22 and 23 is shortened. By way of example, and using FIG.21 as reference, the angle 110 measured between the adjacent sides 13from bends 20 and 21 might decrease to 70-80° with a increase in thecorresponding angles 161 measured at bends 22 and 23 to 100-110°. Thismanipulation of the frame 11 shape serves to add tension in each of thebends, which allows better positioning of the device 10 against thevessel wall 70 while in the deployed configuration, as shown in FIGS.22-25. Additionally, constraining the frame 11 along the first axis 94of the slit 108 allows that distance 146 to be adjusted to provide theoptimum size for the vessel 33 into which the valve 43 is to beimplanted. Assuming a resilient frame 11 is being used that makes thevalve 43 radially expandable, it would normally be preferential toslightly oversize the valve 43 along at the width 146 of the frame 11(along first axis 94) when the valve 43 is in the generally flattenedconfiguration 35, thereby causing the leaflets 78, 79 to relax slightlywhen the valve 43 is in the deployed configuration 36 and beingconstrained slightly by the vessel 33. The proper length of theconstrained frame 11 as measured diagonally between bends 22 and 23 iscalculated such that the leaflets 78, 79 open by an effective amount inthe presence of blood flow 46 that most closely mimics that found in anormal functioning valve.

Dog studies by Karino and Motomiya (Thrombosis Research 36:245-257) havedemonstrated that there is about a 60 to 70% constriction of blood flowthrough the natural valve. In the valve 43 of the present invention, theleaflets 25 should ideally span about 30-60% of the vessel 33 diameteracross. If it is much less than 30%, blood flow 46 may be impeded to anunacceptable degree, while if the leaflets 78, 79 are allowed to fullyopen, they can adhere to the vessel wall 70 and therefore, not closeproperly in the presence of retrograde flow 47. The frame 11 can beformed or constrained such that the distance 146 between points 22, 23lies between nr, which would allow the valve to open to the full extentthat the vessel allows, and 2r in which the valve 43 is stretched tightacross the frame 11 and is very limited in the amount of blood that willallow to pass through. To give the leaflets the flexibility andcompliance to open to permit flow and then close to seal againstbackflow, the slit axis distance 146 of the valve 43 should be oversizedwith respect to the diameter of the vessel into which it is to beplaced. Constraining the valve 43 along the first axis 94 such that itsized a few mm larger than the lower extreme (2r) or a few mm largerthan the upper extreme (πr), not only allows the leaflets to function ina more optimal manner, but also allows the valve 43 to safely andeffectively impinge on the vessel wall to seal and reduce thepossibility of migration. The ideal amount of oversize is largelydependent on the size and diameter of the frame 11 prior to resizing.FIG. 50 depicts a schematic top view of the valve of FIG. 22 showing thelength 147 of the orifice, the width 148 of the orifice, the portion 154of the vessel occluded by a leaflet 25, and the corner gaps 155 thanexist between each lateral edge 156 of the valve orifice 117 and theouter edge 112 of the leaflet 25 (or the frame 11). The followingformula can be to approximate the elliptic circumference (C) of thevalve orifice 117, where a=one half the length 147 of the orifice, andb=one half the width 148 of the orifice 117:

$C = {2{\pi\left\lbrack \frac{\left( {a^{2} + b^{2}} \right)}{2} \right\rbrack}^{1/2}}$

Assuming that we wish to size the valve 43 to produce an orifice 117that opens approximately 30-60% of the vessel lumen 34 (with theoccluded portions 154 comprising 40-70% of the same), the precedingformula can be used to determine the amount of oversize that producesthe desired characteristics. The amount of oversize (valve width 146 inthe flat configuration minus the diameter of the vessel lumen 34) wouldgenerally range from 1-2 mm for smaller valves (those placed in 8-9 mmvessels) up to 3-4 mm for valves intended for larger vessels (17-21 mm).For example, a valve intended for a 14 mm vessel should ideally have a2-3 mm oversize if the range of 30-60% opening is to be maintained. Ifthe frame 11 of a valve 43 having 20 mm sides is constrained such thatthe distance between bends 22 and 23 is adjusted to approximately 16 mm,the valve 43 opens approximately 43%, which is well within the mostdesired range. If constrained to 17 mm, the valve 43 is able to open upto approximately 55% of the vessel diameter. In contrast, over sizingthe valve 43 by 6 mm, produces a large orifice 117 of 83% which liesoutside the target range, although it would certainly produce a valve 43capable of opening and closing in response to fluid flow 46, 47. Toproduce a valve 43 in which the valve width in the generally flattenedconfiguration 35 is 17-18 mm, which would be a valve 43 sized toaccommodate a 14-15 mm vessel, the 20 mm frame 11 should be constrainedsuch that the distance between bends 22 and 23 is 15 mm prior toaddition of the covering 45, if a compliant material such as SIS isused. As depicted in FIG. 26, the frame 11 is constrained across thefirst axis 94 using a temporary constraining mechanism 121, such as bytying a suture through the coil turns 14 of bends 22 and 23 to pull themtoward one another until a distance of 15 mm is reached. After thecovering 45 has been attached, such as by the method previouslydisclosed, the temporary constraining suture 121 is cut, which resultsin a slight expansion in the width of the frame 11 as the SIS stretchesunder the tension of the constrained frame, resulting in the desiredfinal width of 17-18 mm. The amount of expansion varies with thecompliance of the particular covering 45 as well as the resiliency ofthe frame 11. Although the desired final width 146 of the constrainedframe 11 can result from a relatively wide range of initial frame 11sizes, depending on how much the frame is constrained, generally, largersized frames (e.g., sides measuring about 25 mm) are most suitable forlarger vessels (e.g., 16-21 mm in diameter), while smaller frames (e.g.,15 mm) are most suitable for smaller diameter vessels (e.g., 8-9 mm).While this range represents the most common sizes used for correctingvenous valve insufficiency in the lower legs, valves 43 of the presentinvention can be made in a much larger range of sizes to treat veins orother vessels elsewhere in the body.

FIGS. 28-31 depict another embodiment of the present invention in whicha open frame 11, such as depicted in FIG. 28, is assembled into a squareframe (FIGS. 29-31) such the bends 12 are put under tension. Theresiliently tensioned bends 118 in the assembled device (as shown inFIGS. 29-31) result from the initial angle 109 formed in wire frame 11before being assembled into a closed circumference 62 (FIG. 28), beinggreater than the final angle 110. To form the embodiment of FIG. 1, forexample, the wire is wrapped around a pin to form the coil turns 14 withthe sides 13 generally lying about 90° with respect to one another. Theattachment mechanism 15 then secures and closes the frame 11 to form thefinal square shape. In the embodiments of FIGS. 28-31, the first angle109 is made approximately 150°, rather than 90°, which is the desiredfinal angle 110. While the wire is not under stress after the bends 12are initially formed, the bends 12 and sides 13 are stressed when thedevice 10 is constrained during assembly to form the four-sided,generally square shape. In particular reference to FIG. 30, the sides122, 123 adjacent to a resiliently tensioned bend 118 becomes somewhatdeformed when the bend 12 is put under stress, generally assuming abowed shape between the adjacent bends. By creating this ‘roundedsquare’ with tensioned or stressed bends 118, the sides 13 of the frame11 are able to better conform to the rounded vessel wall 70 than would aside 13 that is initially straight prior to deployment. Additionally, byrounding the distal bends 116 of the valve legs 113, it may also reducethe potential for the valve legs 113 to cause trauma to the vessel 33 asthey continue to exert force thereupon.

An additional method of constraining the valve 43, or similar typedevice 10 (e.g., occluder, filter, stent, stent adaptor), is depicted inFIG. 48 in which a circumferentially constraining mechanism (orcircumferential member), 125, is added to at least partially encirclethe frame 11 while it is in both the delivery configuration 37 (FIG. 6)and the deployed configuration 36 such that the device 10 is limited inits ability to radially expand. Once the device reaches its maximalradial expansion, the outward force the device 10 places on the vesselwall 70 is eliminated, thereby reducing potential damage thereto (e.g.,from an improperly sized valve), such as tissue erosion possiblyresulting in eventual perforation of the vessel 33. In the illustrativeembodiment, the circumferentially constraining mechanism 125 comprises asuture that is affixed to and completely encircles the frame 11 to limitthe outward expansion of the valve legs 127, 128. The sides 13 of thevalve legs 127, 128 include an intermediate coil turn 126, alsoillustrated in FIG. 39 fulfilling a different function, that provides aneffective attachment point through which to feed and/or affix the suturerestraint 125. In the illustrative embodiment, the suture restraint 125is in a relaxed state when the device 10 is loaded in the deliverysystem. Then, as the device 10 is deployed, it expands within the vessel33 until it is constrained by the suture restraint 125 if the device 10has been properly sized such that vessel 33 does not provideconstraining forces sufficient to prevent the device 10 from fullyexpanding to its predetermined maximum diameter. If the device isundersized for the diameter of the vessel, it may be subject tomigration due to insufficient expansion. The illustrative embodiment ismerely exemplary of the numerous available circumferentiallyconstraining mechanisms 125. It is not necessary that thecircumferentially constraining mechanism 125 completely encircle thedevice 10. For example, short pieces of suture or another type oftethering mechanism, such as a section of webbing or other material, canbe affixed between the sides of the valve legs to limit their expansion,or the frame can include an integral circumferentially constrainingmechanism 125, such as an expandable strut formed as part of the frame,line 125 of the illustrative embodiment being also representative of aexpanded strut attached to the sides of the frame. The strut wouldunfold as the frame radially expands and limits how far the sides of thevalve leg to which is attached, can spread apart relative to each other,thereby limiting the outward radial force from the device against thevessel wall.

Another possibility is for circumferentially constraining mechanism 125to comprise a sleeve 162 of flexible material, such as SIS around thevalve 43, as depicted in FIG. 49, which is of a diameter appropriate fordeployment within the target vessel 33 (typically, being slightly largerthan the target vessel diameter) that allows the valve to anchorthereto. The sleeve 162 could be affixed to the frame 11 with sutures 50or by some other means as the valve 43 is held in a collapsed conditionprior to loading the device 10, including the sleeve 162, into adelivery system. The sleeve 162 enclosed the length of the valve 43, orthe bends 12 and barbs 16 can be left uncovered, as shown. To reduceresiliency of the sleeve 162, tethers and other types ofcircumferentially constraining mechanism 125 can be used in combinationwith the sleeve 162 to limit radial expandability of the valve 43. Itshould be noted that if the circumferentially constraining mechanism 125itself is a resilient member, it will only serve to reduce the outwardforce of the device 10 against the vessel wall 70 until maximumexpansion is reached.

FIGS. 30-31 depict alternative methods of forming the frame 11 andattaching barbs thereto. In the embodiment shown in FIG. 30, attachmentmechanisms 15, 85 and 84, 86, per side rather than a single cannula asshown in previous embodiments, such as FIG. 29. Rather than placing theattachment mechanisms 15 at the point 87 where the respective ends 60,61 of the wire frame 11 cross to form the square shape, two attachmentmechanisms 15, 85 are placed on either side of the cross point 87.Having an additional attachment mechanism 84, 85, 86 on a side 13provides better fixation of the frame with little additional metal andhelps prevent twisting of the frame 11. On the opposite side whichcontains the double ended barb 39, the double attachment mechanisms 84,86 arrangement provides a similar function. In the embodiment of FIG.31, three attachment mechanisms 15, 85, 88 and 84, 86, 89, are used perside which provide better fixation of the frame 11 as well as serving asattachment points for including supplemental barbs 90, 91, 92, 93 toprovide a more secure anchoring of the device 10 to the vessel wall 70.The illustrative barbs 16 are typically configured such that they extendonly a short distance (less than 1-2 mm) beyond the bends 12; however,the barbs 16 can be made virtually any practical length, such asextending them more than 1 cm beyond the bends 12 to aid in stabilizingthe device 10 upon deployment such that it does not shift laterally andend up being cockeyed within the vessel. To assist in this function, thebarbs can be shaped accordingly, rather than be limited to asubstantially straight configuration.

The present invention is not limited to a two-leaflet valve 43 (ortwo-leg occluder or stent adaptor, etc.). FIGS. 35-40 depictmulti-leaflet valves 43 having three or four valve legs 113 and leaflets25. The addition of additional leaflets reduces the load produced by thefluid column upon each individual leaflet 25. This in turn, puts lessstress upon the sutures or attachment points of the covering 45, therebyallowing the valve 43 to function under higher pressures than wouldotherwise be possible. For example, these valves 43 could proveadvantageous for use on the arterial side, such as to augment pulmonaryvalves, or within the heart itself, where pressures exerted on theleaflets can be significantly higher than normally found on the venousside. FIG. 35 depicts a valve 43 which in the generally flattenedconfiguration 35, has a three legs 127, 128, 130 that lie approximately120° with respect to one another. The respective leaflets are arrangedsuch that the inner edges 111 thereof, define a triangular-shaped valveorifice 117. When the illustrative valve 43 is placed in the vessel 33for which it has been properly sized, as depicted in FIG. 37, theleaflets 78, 79, 119 are able to close against one another to seal thevalve. The concept of adding additional legs 113 to distribute the loadover a larger number of attachment points 50 (e.g., sutures) and addpositional stability to the device 10, can be applied to occluders andstent adaptors as well.

One method of forming the embodiment of FIG. 35, involves constructing atriangular-shaped frame 11, as shown in FIG. 36, that includes anintermediate coiled eyelet 132 formed at the midpoint of each of thethree sides 13. A temporary constraining suture 121, such as that shownin FIG. 38, is threaded through each of the intermediate eyelets 132,drawing them inward to form three additional bends 133, 134, 135 formingthree legs 127, 128, 130 of a desired shape (FIG. 35), depending howtightly the constraining suture 121 is drawn. At this point, thecovering 45 is attached to the frame 11, either as three separateleaflets 78, 79, 119, or a single piece through which thetriangular-shaped valve orifice 117 is formed. After the covering 45 hasbeen secured to the frame 11, the constraining suture 121 is cut andremoved. As depicted, the barbs 16 are affixed to the triangular shapedframe of FIG. 36, two per side, such that they terminate on either sideof intermediate eyelet 132. Thus, when the intermediate eyelets 132 aredrawn inward to create six sides 13, each includes a barb 16.

The embodiment of FIGS. 38-40, which includes four legs 127, 128, 130,131, is formed in a similar manner to that of the embodiment of FIGS.35-37. The frame 11 is initially formed in a square configuration (FIG.39) with intermediately placed coiled eyelets 132 at the midpoint ofeach side 13, dividing the side into a first and second side portion137, 138. As depicted in FIG. 38, the temporary constraining suture 121is used to draw the eyelets inward where they form the four additionalbends 133, 134, 135, 136 such that four valve legs 127, 128, 130, 131are formed with the first and second sides portions 137, 138 becomingsides 13 of adjacent valve legs 127, 128. A square-shaped valve orifice117 is created when the four leaflets 78, 79, 119, 120 are attached tothe legs 127, 128, 130, 131 of frame 11. One should appreciate thatvalves with more than four legs would be made in a similar manner to theembodiments above with a five-sided valve being formed from a pentagon,a six-sided valve being formed from a hexagon, etc.

Delivery of the device 10 of the present invention can be accomplishedin a variety of ways. One method, depicted in FIG. 33, involves the useof a delivery system 103 similar to that used to deliver embolizationcoils. The delivery system 103 comprises an outer member 105, such as acannula or catheter, and an coaxial inner member 105 that includes atethering tip 107, such as a notched cannula, adapted to receive a barb17 extending from the frame 11. The tip 104 of the barb is configuredsuch that it can positively engage with the tethering tip 107. This canbe accomplished by adding a projection, such as a secondary barb, hook,spine, etc. to the tip 104, or otherwise enlarging the diameter thereofsuch that it can be releasably secured by the tethering tip 107 untildeployment. The coaxial inner member 106 also includes an outer sheath149 that retains and the locks the barb tip 104 within the tethering tip107 until it is advanced or retracted by manipulation of a proximalhandle (not shown) to expose the notch 150 in the tethering tip, whichreleases the barb 17 and deploys the device 10. The device 10 ispreloaded within the outer member 105. The coaxial inner member 106 andattached device 10 are then advanced together from the outer member 106at the target site. Further manipulation of the proximal handle,advances the tethering tip 107, which in this particular embodiment,includes a coiled spring 151, relative to the outer sheath 149. Afterthe device 10 has been released from the tethering tip 107, thespring-activated handle is released and the outer sheath 149 slides backover the tethering tip 107. The coaxial inner member 106 is withdrawninto the outer member 105 and the entire delivery system 103 is removedfrom the patient. As shown in FIG. 33, the barb tip 104 extends justbeyond the coil turn 14 of the frame 11 so as to have sufficient room toengage with the coaxial inner member 106. The barb tip 104 must bepositioned to account for whether the device 10 is to be placed using afemoral approach or a superior approach.

The illustrative delivery system 103 represents only one of manypossibilities. For example, the device 10 can be attached to a deliverydevice using screws, clips, magnets, or some other tethering mechanism,or can be deployed by applying electrical current, heat, or some othermeans to cause detachment with a carrying mechanism. As previouslydisclosed, rather than making the device 10 self-expanding, where it ispushed from some sort tubular device, it can be formed from a ductilematerial, mounted over a balloon or other inflatable or expandabledelivery mechanism, and deployed by expanding the device in that manner.

The illustrative valve embodiments having a simple four-bend serpentineframe, such as the one depicted in FIG. 21, advantageously limit theamount of metal being placed into the vessel. This is thought to helpreduce the risk of thrombus formation, as well as allow the device toassume a smaller profile in the delivery system. Because thisconfiguration lacks some of the longitudinal stability of a frame havingadditional points of contact with the vessel wall (e.g., at least 4-6 ateach end), there is a greater risk of the valve being deployedoff-center, such as depicted in FIGS. 51 and 52, wherein thelongitudinal axis of the valve does not coincide with the longitudinalaxis of the vessel. Titling is often the result of particular bendexerts more force than others, causing the bends to become pivot pointsthat cause longitudinal shifting of the valve prosthesis. This, ofcourse, results in the opening 117 of the valve being located off-centerwith respect to the vessel 33, which may result in the function of theleaflets 78, 79 being impaired such that the valve will not properlyopen and close in response to blood flow and/or blood may poolexcessively (not clear itself) in certain locations along the base ofthe leaflets, leading to thrombus formation. When the leaflets compriseremodelable biomaterials, such as SIS and other ECM materials,off-center deployment can result in one or more leaflets broadlycontacting the vessel wall, which could result in tissue ingrowthaffecting the ability of the leaflet(s) to function and coapt with otherleaflets. Thus, a centered orifice (e.g., the point along which theleaflets coapt or otherwise contact or seal against one another) isgenerally considered the optimum configuration in a multi-leaflet valve.Even six bend stent designs (three bends oriented at each end) have beenshown to be longitudinally unstable. Generally, longitudinally stabilitybecomes less of an issue once there are four bends or more oriented at aparticular end of the stent frame so that tilting is less likely tooccur, although it is not necessarily desirable to have a four leggedvalve to address the tilting problem.

One method of addressing the problem is in the design of the deliverysystem, while another involves modification of the valve that haveadditional structure attached to the legs of the valve to FIGS. 53-71depict various embodiments of the present invention in which the valve43 includes a centering support element 164 configured to contact thevessel wall in a manner to support and help properly align with thevessel, the basic valve portion 43 which in these particularembodiments, comprises a generally saddle-shaped, serpentineconfiguration that includes a pair of co-aptable leaflets 78, 79 thatdefine an opening between two bends 20, 21 comprising the first end 68of the valve 43, the outer edges 112 of the leaflets comprising a frame11 or resilient portion that allows the valve portion to form a sealaround the entire circumference of the vessel, such that the leafletmaterial, preferably an ECM such as SIS, is in direct contact with thevessel wall. The centering support structure 164 is defined as a singleelement or plurality of elements attached to, or integral with, thevalve portion 43 and which include one or more contact points 167 thatengage the vessel walls such that upon deployment, the valve portion 43is largely prevented from tilting relative to the longitudinal axis 162of the vessel, as depicted in FIGS. 50-51, so that the opening 117 ofthe valve is generally centered thereinside.

The centering support structure 164 of the present invention falls intotwo general categories. Devices 10 of the first group include supportstructure 164, such as second and/or third frames 31, 32, an adjoiningstent 219 or other expandable or inflatable elements, that are connectedto, or integral with, the basic valve portion 43, and that are eitherattached to the proximal end, distal end, or both ends thereof. Suchsupporting structure 164 functions by either expanding or deployingwithin the vessel in advance of the valve portion such that the valveportion is less likely to tilt off-center when it fully expands, or bytrailing or following the valve portion 43 out of the delivery system sothat as the valve portion deploys, the centering support structure 164remains within or attached to the delivery system to help longitudinallyalign the valve portion within the vessel until the support structure164 deploys as well, as well as to prevent the valve from ‘jumping’ fromthe delivery system.

An example of a device 10 having the first type of centering supportstructure 164 is depicted in FIG. 53, in which the centering support isprovided by a second frame 31, of the same type of the valve portion 43,attached to the valve portion by an attachment mechanism 171 such assutures, where points 169 and 170 of the second frame 31 to bends 22 and23, respectively. When the device 10 is deployed from the deliverysystem such that the second frame 31 is allowed to expand within vessel33, the two arms 165, 166 comprising the second frame expands to contactthe vessel walls 70 at points 167 and 168 located at the proximal endsof respective arms 165, 166 and the first or proximal end 68 of thedevice 10, the lateral arms basically providing a structure mirror ofthe two legs 127, 128 of the valve. In the illustrative embodiment, thecentering support structure 164 includes a pair of barbs 172 extendingfrom each of the arms 165, 166 to further secure the device and preventmigration.

Following deployment of the leading second frame 31, the valve portion43 is still within or secured by the delivery system, helping tomaintain the second frame 31 in a longitudinally stable position. Whenthe valve portion is deployed 43, the second frame 31, already securedin the vessel 33, provides an anchor to prevent the valve portion 43from tilting off center as the latter expands and lodges within thevessel.

FIG. 54 depicts an embodiment in which the valve portion 43 and secondframe 31 are reversed with points 170 and 171 of the second frame beingattached to bends 20 and 21, respectively, at the second or distal endof the valve portion. As the valve portion 43 is deployed, the secondframe 31 remains within or affixed to the delivery system, thus reducingthe likelihood of the valve portion 43 being deployed off-center withrespect to the longitudinal axis of the vessel. Once the second frame31, the remainder of the device 10, is deployed, the valve portion 43 isalready positioned in the vessel, being anchored and maintainedlongitudinally stable by the second frame until it too is deployed,wherein the valve portion 43 in turn, provides anchoring support of thesecond frame to prevent it from tilting. FIG. 55 depicts an embodimentthat includes both a second frame 31 attached to the first end 68 of thevalve portion 43 and a third frame 32 attached to the second end 69thereof. Thus, the device 10 receives the centering and stabilizationbenefits of both centering support structure 164 components.

Besides having the centering support structure 164 comprise second andthird frames 31, 32 of the same basic four-bend serpentine design, FIGS.56-57, 66-67, and 71-75 depict alternative structure that can be affixedto, or extend from, one or both ends 68, 69 of the valve portion 43.FIGS. 56-57 depict an adjoining serpentine or zig-zag stent 219, such asa Gianturco Z-STENT™ (Cook Incorporated) that is attached with suture171 to the bends 22, 23 located at the first end 68 of the stent. Aswith each of the embodiments, alternative attachment 171 methods can beused, such as ring fasteners, plastic bands, struts, etc. Theillustrative adjoining stents 219 include a first radial constraint 176(which is optional), such as the illustrative suture, at the second end224 of the adjoining stent 219 to constrain contact points 177 and 178by threading the suture 176 therethrough, along with the attachmentpoints 169, 170 of the adjoining stent 219 which are connected to bends22 and 23 of the valve portion 43, then drawing the points inward. Inthe embodiment of FIG. 57, and second radial constraint 181 is includedat the first end 223 of the adjoining stent 219 which constrains thefour contact points 167, 168, 179, 180 located at that end. Theillustrative zig-zag stent 219 includes four points at each end;however, any number of points or configuration that allows attachment tothe valve portion 43 may be used.

An alternative method of manufacturing the same basic configurations ofthe embodiments of FIGS. 53-57 is to cut or otherwise form both thevalve portion frame 11 and the centering support structure 164 out of asingle piece of cannula, such as nitinol, stainless steel, or anothersuitable stent material. FIG. 83 depicts a cannula-formed embodiment ofa valve prosthesis 10 that is similar to the wire-formed versiondepicted in FIGS. 56-57, which include one or more constraining devices176, 181, not present in the embodiment of FIG. 83, to constrain one orboth ends of the adjoining Z-stent portion 219. The illustrativeembodiment of FIG. 83 is cut from a nitinol cannula of thickness suchthat electropolishing result in a strut width of 0.009″. The exemplarystrut widths for 14.0 mm and 16.5 mm diameter valve prostheses 10 isalso about 0.009″ width. The valve portion frame 11 and the Z-stentportion 219 are interconnected by a pair of 0.0144″ thick strutsextending from the opposing proximal/top bends of the valve portionIntergral barbs 172 extend from the proximal bends of the centeringsupport structure 164/adjoining frame 210. Integral barbs 124 alsoextend from the distal/bottom bends of legs 127, 128.

Another related embodiment is depicted in FIG. 66 in which the adjoiningstent 219 comprising the centering support structure 164 is a cannulastent such as the illustrative PALMAZ® Balloon Expandable Stent (CordisCorp., Miami Lakes, Fla.) that is integrally attached to the first end68 of the stent portion 43 via a short strut 199. Both the frame 11 ofthe valve portion 43 and the centering support structure 164 are cut orformed from a single piece of cannula using any well-know method offorming a pattern into a cannula (e.g., laser). FIG. 67 depicts anillustrative embodiment wherein the centering support structure 164basically mirrors that of the stent portion frame 11, with theattachment 199 therebetween also being a short strut. Integral barb 172are located on the centering support structure to help anchor theprosthesis in the vessel. FIG. 72 depicts still another embodiment inwhich the both the stent portion frame 11 and the centering supportstructure 164 are formed from the same piece of cannula; however, thesupport structure 164 comprises an adjoining zig-zag stent 219. Anoptional feature of the embodiment of FIG. 72 are covering attachmenttabs or barbs 201 distributed along the frame 11 of the stent portion,which each comprise an integral sharp projection extending from theframe 11 to help secure the covering or leaflets (not depicted) there.These tabs 201 represent an alternative or additional means of fixationto sutures.

FIG. 71 depicts yet another alternative embodiment of centering supportstructure 164 comprising an expandable helical structure 200 or springthat extends from the second end 69 of the valve portion 43. The helicalstructure 200 functions much like the aforementioned second frame oradjoining stent to remain coupled with the delivery system to helpcenter the valve portion 43 within the vessel and/or prevent jumping ofthe valve. A further example of centering support structure 164extending from the second end 69 of the valve portion is depicted inFIGS. 73-74 wherein the valve portion 43, which is cut, etched, orotherwise formed from a sheet of metals stock 152 (FIG. 73). When theframe 11 is formed into the second configuration 36, as shown in FIG.74, the distal projections 203 are brought into close proximity to oneanother and become the last portion of the device 10 to be deployed fromthe delivery catheter 26. This allows the valve portion 43 to expandupon deployment, while still tethered to the delivery catheter or sheath26 (FIG. 74), until the distal projections 203 exits the passageway ofthe delivery catheter 26, thus helping to maintain the longitudinalalignment of the valve portion 43 as it engages the vessel wall. In theillustrative embodiment, a pair of integral barbs 124 extend from bends22 and 23 for anchoring the valve portion 43, while the elongateprojection 203 also includes an optional barb 204 for both securing thedevice within the vessel and providing resistance against the inner wallof the delivery system 26 to control the tendency of the device 10 toprematurely deploy when the majority of the valve portion 43 has exitedthe passageway. It should be noted that where the centering supportstructure 164 of the exemplary embodiments is shown extending from aparticular end or another of the valve portion 43, in most instances,the support structure 164 could be easily adapted to extend from theopposite end as well.

FIG. 75 depicts an embodiment of the present invention that includesboth an adjoining stent 219 to provide centering support, such as theillustrative zig-zag stent, as well as an outer proximal sleeve 229 thatextends proximally (or upward) from the valve portion 43 and providesthe attachment means 199 to the adjoining stent 219, which in theillustrative example is sewn to the first end 231 of the proximal sleeve229 such that the stent and valve portion frames 11 do not have metal tometal contact. The second end 232 of the sleeve 229 is then attached tothe valve potion 43 using sutures 50 or another well-known means. Theproximal sleeve 229, which in the illustrative embodiment has thepossible advantage of not covering the vessel wall in the region betweenthe two legs 127, 128 of the valve portion 43, could optionally comprisea complete cylindrical sleeve, such as the embodiment of FIG. 49.Optionally, the adjoining stent 219, or a second adjoining stent, couldbe attached to the second end 232 of the sleeve 219 if so configured.The proximal outer sleeve is preferably made of a low ornon-thrombogenic biomaterial, such as SIS or another ECM. The number,configuration, and arrangement of anchoring barbs 16 can vary accordingto use and device configuration. In the illustrative embodiment, aseries of barbs 230 are attached to the struts of the adjoining zig-zagstent 219, with the valve portion 43 including another series of barbs17, 18, 71, 72, as well.

A second strategy for providing better longitudinal centering supportfor the valve portion 43 involves the placement of the centering supportstructure 164, such that it extends laterally from the valve portionframe 11, rather than extending from one or both ends thereof. FIG. 58depicts a side view of a device 10 that includes a pair of lateral armsor wings 165, 166, comprising struts attached to the frame 11 of thevalve portion 43. The arms 165, 166, typically similar in configurationto the legs 127, 128 of the valve 43, extend laterally, followingdeployment, to provide two supplemental contact points 167, 168 thathelp provide longitudinal support and reduce the likelihood that thevalve portion 43 would tilt off center longitudinally during orfollowing deployment. The lateral arms 165, 166 advantageously liebetween the leaflets 78, 79 and the adjacent vessel wall, therebyoffering protection from the leaflets possibly adhering to the vesselwall 70, which could lead to failure of the valve leaflets to close orcoapt properly during retrograde flow. This problem may be even morelikely to occur when the valve is not properly sized (e.g., oversizing)with respect to the vessel. The use of remodelable biomaterials, such asSIS, can further lead to permanent adherence of the leaflets to thevessel wall if the valve is not configured or sized properly for thevessel, thus the lateral elements can be especially advantageous inthese particular embodiments.

The basic embodiment of FIG. 58 can be formed in a number of differentways, with selected examples depicted in FIGS. 59-61. The frame 11 ofthe embodiment of FIG. 59 comprises four components. The lateral arms165, 166 each comprise part of a closed diamond-shape component 182,183. For example, lateral arm 166 includes four bends l68, 186, 187,188, with bend 168 comprising the contact point of the lateral arm 166and bend 186 forming the bend 20 of the valve leg 128. To permit the arm166 to extend outward from the valve portion 43 (shown without leaflets)so that it is able to help in centering, bends 187 and 188 deformed in adifferent plane, such that the closed frame 182 is bent along an axis189 intersecting both bends. The angle of the bend should be such thatthe contact point 167, 168 exert a safe, but effective pressure againstthe vessel wall when the valve is in the deployed configuration 36, suchthat the valve 43 is unlikely to tilt. Each closed section 182, 183 isattached to a pair of V-shaped sections 184, 185 which each include abend 22, 23 that together, comprise, the first end 68 of the valveportion 43. It should be noted that the term ‘V-shaped’ also includesthe concept of a rounded ‘V’ or ‘U-shaped’ section as well. Thecomponents 182, 183, 184, 185 can be joined by soldered cannulae, laseror spot welding, or some other well-known means of joining a metalframe. Once assembled into a closed frame 11 having lateral arms 165,166 comprising the centering support structure 164, the ends of theV-shaped sections can serve as anchoring barbs 16 to secure the valve 43following deployment.

FIG. 60 depicts an alternative assembly of the basic embodiment of FIG.58. Like the embodiment of FIG. 59, the device 10 includes two V-shapedsection 184, 185, which in the illustrative embodiment comprise the twolegs 127, 128 of the valve portion 43. The remaining component comprisesa serpentine portion 192 which comprises an eight-bend zig-zag stent inwhich two of the points 167, 168 (those oriented toward the first end68), and their adjacent struts, form the arms 165, 166 comprising thecentering support structure 164. The other two points of the serpentineportion 192, adjacent to points 167 and 168, comprise bends 22 and 23 ofthe valve portion 43, when the components are assembled. The ends of theV-shaped sections 184, 185 form barbs 16 at the first end 68 of thedevice. Optionally, separate barbs can be attached to the frame 11, suchas using the illustrative cannulae 15, if barbs are desired at thesecond end 69.

A third embodiment, similar to those of FIGS. 59 and 60, is depicted inFIG. 61. In this embodiment, the valve portion 43 is basically the sameserpentine frame 11 configuration as most of the illustrative valveembodiments (excluding those of FIGS. 59 and 60). The arms 165, 166comprising the centering support structure 164 each include a pair ofattachment struts 190, 191 that lie parallel to the legs 127, 128 andare attached to the frame 11 thereof, using cannulae (now shown),welding, or another well-known method. The open ends of the attachmentstruts 190, 191 serve as barbs 16 extending from the first end 68 in theillustrative embodiment. It should be noted that the components of theembodiments of FIGS. 58-61 can either be made of the same material andstrut thickness, or they can be formed of different materials. Forexample, in the embodiment of FIG. 61, the valve portion 43 frame 11might be made of spring stainless steel, while the arms 165, 166 aremade of nitinol or a smaller gauge of stainless steel wire.Additionally, the arms 165, 166 might be made of bioresorbable materialor biomaterial which would help center the valve portion, then beresorbed or disappear after the valve has stabilized and thus, beunlikely to tilt, or if adherence of the leaflets to the vessel is not aconcern.

FIG. 65 depicts an embodiment similar to that of FIG. 61 except that thearms 165, 166 are configured such that they include both a first contactpoint 166, 167 and a second contact point 179, 189 that each contact thevessel wall 70 for further stability. The M-shaped arms 165, 166 (theportion extending outward from the valve portion 43) further include apair of attachment struts 190, 191 that are affixed to the valve portionframe 11 and may extend outward to form anchoring barbs 16.

FIGS. 62-62A depict similar embodiments of the present invention inwhich the centering support structure 164 includes both a set of lateralarms 165, 166 as in the previous embodiments, along with a pair ofsupplemental legs 193, 194 for additional longitudinal support. In theembodiment of FIG. 62, the device 10 comprises a first and a secondserpentine elements or zig-zag stent portions 174, 226 attached end toend using an attachment mechanism 199 such as suture. The legs 127, 128then span both zig-zag portions 174, 226, such that bends 22 and 23,located at the first end of the valve portion 43, are part of the firstzig-zag portion 174, while bends 20 and 21, located at the second end 69of the valve portion 43, are part of the second zig-zag portion 226. Theembodiment of FIG. 62A comprises a single frame 11 which also forms thelateral arms 165, 166 and the supplemental legs 193, 194, as well as thelegs 127, 128 of the valve portion 43. The legs include a loop 227located midway on the sides 13 that provide an attachment point to thecrossing struts of lateral arms 165, 166 supplemental legs 193, 194,which optionally include attachment loops 227.

The embodiments of FIGS. 62-62A are but two examples of a method offorming a valve portion 43 having two lateral arms 165, 166 and twosupplemental legs 193, 194. FIG. 80 depicts a frame 11 of yet anotherembodiment whereby the first and second serpentine elements 173, 226 arejoined by a series of elongate valve leg struts 225 that are attached toselected struts 238 of the serpentine elements 173, 226 with cannulae 15or another well-known method of bonding such that the individualserpentine sections 240 across the two serpentine elements 173, 226 formthe legs 127, 128 of the valve 43 to which the leaflets 78, 79 areattached (similar to that depicted in FIG. 62). For purposes of thepresent disclosure, a serpentine section 240 is defined as a bend 237and the accompanying struts 238 that originate therefrom to assume aV-shape component, which connects to adjacent bends 245 oriented in theopposite direction to form the ‘zig-zag’ or ‘Z’ or ‘S’ configuration. Inaddition to comprising the attachment mechanism 171 that joins the twoserpentine elements 173, 226, the leg struts also provide added rigidityto the legs 127, 128 and frame 11 so that the weight of column of bloodacting on the leaflets is less likely to cause the top bends 22, 23 tobe pulled inward toward one another, thereby changing the shape of thevalve 43, which could affect the coaptation of the leaflets (how wellthey fit together or contact one another) and perhaps, lessen the radialpressure or force being applied against the vessel wall. Furthermore,the leg struts 225 may be conveniently extended beyond each of the bends20, 21, 22, 23 such that they form a series of eight barbs (two at eachbend with four oriented in the proximal direction and four in the distaldirection, to anchor the device 10 following deployment.

Unlike embodiments of the present invention in which the frame 11 can beflattened to facilitate attachment of the covering or leaflets, thecovering must be attached to the tubular-shaped illustrative embodimentsof FIGS. 62-62A and 80, and others, by another means. One exemplarymethod includes introducing a wedge or chisel-shaped mandril into thelumen of the device over which a wet, diamond-shaped piece SIS or othercovering 45 is placed such that it conforms and assumes itscharacteristic saddle-shaped configuration. The covering is closelyaligned with the frame 11 of the valve portion, then the covering 45 isattached along the axis that includes the orifice 117 by hooking thebarbs 16 located at bends 22 and 23 therethrough. The covering 45 isthen attached in a similar manner using the barbs 16 at ends 20 and 21.The mandril diameter is controlled to result in a deployed valve thatproduces the desired amount of coaptation of the leaflets and otherperformance characteristics. The covering is then sutured in the mannersimilar to that depicted in FIGS. 26-26A. To attach the covering aroundthat point which the lateral arms 165, 166 and supplemental legs 193,194 extend from the frame 11, a slit is made a corresponding point alongthe covering that allows the struts to emerge, then the covering iswrapped therearound and secured in place. After the covering has dried,it is slit along the short axis to form the orifice, preferably leavinga 1-2 mm gap of covering remaining between the bend 12 and the edge ofthe orifice 117 to help prevent reflux at the corner bends 22, 23. Themandril may be removed before or after the drying process.

Referring now to FIGS. 80 and 81, the lateral arms 165, 166 andsupplemental legs 193, 194 that comprise the centering support structure164 in the illustrative embodiment are made up of serpentine sections440 comprising alternating lateral arm serpentine sections 236 and valveleg serpentine sections 235, the latter comprising a portion of theframe 11 supporting the two legs 127, 128. In the illustrativeembodiment, the valve leg serpentine sections 235 are longer than thelateral arms section 236 (and lateral arms 165, 166). For example, thestruts 238 of the lateral arm serpentine sections 236 may be 12 mm, asopposed to 15 mm for the struts 238 of the longer serpentine sections235. Shortening the lateral arms 165, 166 and supplemental legs 193, 194relative to the adjacent serpentine sections 235, helps keep the ends167, 168, 241, 242 thereof away from the bends 20, 21, 22, 23 and barbs16 of the valve portion 43 for easier loading and less chance ofentanglement during deployment. Conversely, the lateral arms 165, 166and/or supplement legs 193, 194 can be made longer (e.g., 20%) to alsoavoid having the ends becoming ensnared with barbs. A further advantageof a longer lateral arm 165, 166 is that the leaflets 78, 79, as theyopen and are folded back during valve function, cannot become caught onthe contact points 167, 168, which in the case of the longer arms, iswell above the reach of the leaflets.

In addition to varying the length of the serpentine sections 235, 236 tochange the performance characteristics of the valve 43 (with leafletsnot shown), the width 243 of the respective sections 235, 236 can bevaried, as well as the angle 239 formed by the bend 237 bend 12 (eyelet)diameters, and struts 238, to create a valve that exerts the desiredradial pressure against the vessel such that it properly seals with thevessel without causing erosion of vessel wall tissue due to excessforce. These dimensions can be changed to maintain a constant radialpressure across the range of different valve sizes. Furthermore, thesedimensions can be manipulated to produce other desired characteristics,such as minimizing the amount of plastic deformation the frame 11undergoes upon being loaded into the delivery system. In theillustrative artificial venous valve embodiment, the preferred range ofthe frame 11 wire thickness is 0.003-0.030″, with a more preferred rangeof 0.0075-0.015″ and most preferred range of 0.008-0.012″. The preferredeyelet diameter at the bends 15, 237 is 0.005-0.150″, with a morepreferred range of 0.010-0.060″ and a most preferred range of0.015-0.040″. The length of the strut 238 of the valve leg serpentinesection 235 is preferably 3-25 mm, with a more preferred range of 7-16mm. The lateral arm serpentine section 236 is preferably 3-30 mm, with amore preferred range of 5-19 mm. Preferably, the struts 238 of thelateral arm serpentine section 236 should be about 80% of the valve legserpentine section 235 or 20% longer, to give the desired amount ofoffset to avoid entanglement. Referring also to FIG. 62, the overalllength of the illustrative device 10 (combined serpentine stents 173 and226) should preferably be 1-2× the vein diameter, with a more preferredrange of 1.5-2×. The valve covering 45 is sized so that the orifice 117is able to open to 10-120% of the vein diameter, with a more preferredrange being 60-100%. The preferred range of the amount of coaptation orcontact of the leaflets 78, 79 is 5-150% of the diameter of vein wherethe valve is implanted, with a more preferred range of 10-50%

FIG. 82 depicts a flattened portion of a first or second serpentinestent 173 in which the struts 238 are plastically deformed into a curvedconfiguration 244 such that the serpentine sections 240 are more roundedand are able to better conform to the vessel wall. To maximize orpreserve the curvature of the struts 238, the cannulae 15 attaching thevalve strut 238 (as depicted in FIG. 80) can be located more toward thecenter of the respective struts 238 being joined. Otherwise, only theportions of the struts 238 about the bends 237 would assume the roundedor curved configuration 244 in the assembled device 10.

FIG. 84 depicts a cannula-formed version of the general configuration ofthe embodiments of FIGS. 61, 62A, 62B, and 80. The illustrative nitinolframe 11 with centering support structure 164 comprise a pair ofadjoining serpentine row sections 248 laser cut from nitinol cannula andelectropolished to produce struts having a thickness and width of 0.006″(for the 14.0 and 16.5 mm diameter embodiments). The two sections 11,164 are interconnected by a short strut. The SIS material 58 is foldedover and sewn to obliquely opposite struts of both adjoining serpentinerow sections 248 so that each leaflet 78, 79 entirely spans bothsections with a notch 249 being formed in the material, whereby thematerial is wrapped around the strut 199 to maintain an leaflet outeredge 112 than engages the vessel wall. The optimal strut dimensions aredependent on several design factors. For example, the struts may be madethicker (e.g. 0.009″) if the strut length is decreased. In the nitinolembodiment, the struts (sides 13) advantageous assume a slightserpentine configuration as the prosthesis is deployed. This producesbetter contact with the vessel wall than a straight wire strut, whichallows for a better seal and facilitates remodeling of the ECM material.As with the similar wire-frame embodiments, two arms 165, 166 extendlaterally from the two legs 127, 128 that carry the support frame 11which comprises portions of both serpentine row sections 248. Similarly,two additional supplemental arms or legs 174, 175 interconnect the twolegs 127, 128 and provide additional longitudinal stability. It shouldbe noted that the serpentine row sections 248, although separate ‘Z’stent units in this particular embodiment, can comprise any combinationof struts or sections that produce a characteristic ‘Z’ stentconfiguration (of any number of bends) or an adjoining ‘Z’ stentconfiguration (e.g., FIGS. 62-62A).

Additional embodiments in which the leaflets span more than oneserpentine segment 248 are depicted in FIGS. 85-86. In the embodimentFIG. 85, the leaflets 78, 79 extend over the top three serpentine rowsections 248 of the valve prosthesis such that struts of eachcollectively form the frame 11 of the valve portion 43. In theillustrative embodiment, the valve material 58 is sutured around theframe 11 so that it is able to directly engage the vessel wall. Theremaining interconnecting struts and cells 247 form the centeringsupport structure 164 with lateral arms 165, 166 of the top serpentinerow section 248 also serving as protection against the leaflets adheringto the vessel wall, which could cause loss of function. FIG. 86 depictsa related embodiment in which the leaflets 78, 79 span four consecutiveserpentine row sections 248 of the valve prosthesis support frame (theframe 11 plus centering support structure 164). The lateral armstructure 165, 166 forms the same function as those in the embodiment ofFIG. 85, although they include more struts and bends by virtue of thevalve prosthesis support frame geometry. The number of serpentine rowsections that the leaflets span can be varied to advantageouslymanipulate the angle that the leaflets assume relative to thelongitudinal axis of the vessel. For example, the illustrative four-rowleaflet embodiment of FIG. 86 includes a steeper leaflet angle than thethree-row embodiment of FIG. 85. The leaflets angles may also beadjusted by manipulating the stent geometry (e.g., strut length, numberof bends/points as measured circumferentially, etc.). For example, it ispossible that a four-row leaflet could have a smaller (shallower) anglethan certain three-row embodiments, depending on the support framegeometry. Both embodiment include integral barbs 124 at the first end 68of the valve portion 43 and integral barbs 172 located on the centeringsupport structure 164. It should be noted that the leaflets can beconfigured to span an even greater number of serpentine row sectionsthat those embodiments illustrated. Furthermore, the leaflets can beplace anywhere on the valve prosthesis support frame. For prosthesiscould be formed such that there are uncovered serpentine row sectionsabove the leaflets (or both above and below).

FIGS. 63-64 depict valve embodiments in which frame 11 and centeringsupport structure 164 are part of common structure comprising a firstserpentine or zig-zag stent 173. In the embodiment of FIG. 63, theeight-point zig-zag frame includes four distal 20, 20′, 21, 21′ and fourproximal 22, 23, 165, 166 bends. The struts or sides 13 that connectpoints 22 and 23 provide the frame 11 support of the leaflets 78, 79.Rather than supporting the entirety of each leaflet 78, 79, the distalor bottom edges 196 thereof are not reinforced by the frame 11. Anoptional supplemental frame (not shown) may be included to reinforce thedistal edges 196 and give it added resiliency for sealing against thevessel wall. FIG. 64 depicts a similar embodiment to that of FIG. 63 inwhich the frame 11 and centering support structure 164 are atwelve-point zig-zag stent, such that there are both first 165, 166 andsecond 174, 175 pairs of arms. The distal or bottom edge 196 of eachleaflet 78, 79 is attached to a distal contact point 198. As with theembodiment of FIG. 63, the distal edge 196 can be made resilient by theaddition of a wire or other materials that help it provide a better sealagainst the vessel wall.

FIG. 68 depicts an valve embodiment that is related to that of FIG. 49in which the valve portion 43 includes a circumferentially constrainingmechanism 125. Unlike the sleeve or material depicted in FIG. 49, thecircumferentially constraining mechanism 125 of FIG. 68 embodimentcomprises a radially expandable or self-expanding stent, such as theillustrative ZILVER™ Stent (Cook Incorporated) which is made of asuperelastic NiTi alloy. In the illustrative embodiment thecircumferentially constraining mechanism 125 is particularly adapted toserve as a centering support structure 164, although even the materialsleeve of FIG. 49 would offer a similar benefit, as well. The valveportion 43 can either be sized to fit within the outer stent such thatit would not migrate, once deployed, or the legs 127, 128 could besutured or otherwise affixed to the legs using an attachment mechanism171 to ensure that the valve portion 43 does not move relative to theconstraining mechanism 125.

FIGS. 69-70 an embodiment of the present invention that is formed from asheet of material 152, such as stainless steel, nitinol, etc., by lasercutting, stamping, machining, etching, or some other well-known method,wherein the design includes a valve portion 43 and integral centeringsupport structure 164 that is folded or otherwise reshaped from theflat, first configuration 35 into the second, deployed configuration 36.In the embodiment of FIGS. 69-70, the centering support structure 164comprises a pair of opposing arms 165, 166 that extend outward when thedevice 10 is in the deployment configuration 36 such that they form acircular ring configured to support the valve portion 43 and prevent itfrom tilting within the vessel. In the illustrative embodiment, thecentering support structure 164 is attached to the frame 11 of the valveportion 43 by a pair of short struts 199. One or more optional flexiblezones 227, that comprise bends in the frame 11, may be incorporatedthereinto to for the purpose of providing better conformity of the frameto the vessel.

1. A valve prosthesis for implantation within a vascular vessel,comprising: a support frame supporting two or more leaflets, the two ormore leaflets including a co-aptation position and cooperatively forminga valve orifice, at least a portion of the support frame supporting eachof the two or more leaflets at a point adjacent the valve orifice; eachof the two or more leaflets including opposing proximal and distalleaflet surfaces and first and second outer edges; the support frame andleaflets together functional as a valve to restrict blood flow in afirst direction when implanted in the vascular vessel; the support framecomprising frame elements around which the first and second outer edgesof the two or more leaflets are wrapped to allow the first and secondouter edges of each of the two or more leaflets to non-circumferentiallyengage a wall of the vascular vessel such that the frame elements arenon-centering of the co-aptation position within the vascular vessel;and at least one centering support element configured to center theco-aptation position within the vascular vessel, each of the at leastone centering support element attached to the frame elements only at oneor more points adjacent the two or more leaflets and including a portionthat traverses one of the two or more leaflets from the first outer edgeto the second outer edge and is free of contact with the proximalleaflet surface and the distal leaflet surface of one of the two or moreleaflets; wherein the support frame comprises a first serpentine sectionhaving first and second opposing bends positioned at a first end of saidvalve prosthesis and third and fourth opposing bends positioned at asecond, opposite end of said valve prosthesis, said first and secondopposing bends lying on a first transverse axis of said valve prosthesisand said third and fourth opposing bends lying on a second transverseaxis of said valve prosthesis; wherein the at least one centeringsupport element comprises a centering support frame comprising a secondserpentine section having fifth and sixth opposing bends positioned atthe first end of said valve prosthesis and seventh and eighth opposingbends positioned at the second, opposite end of said valve prosthesis,said fifth and sixth opposing bends lying on a third transverse axis ofsaid valve prosthesis and said seventh and eighth opposing bends lyingon a fourth transverse axis of said valve prosthesis; wherein the firsttransverse axis is substantially perpendicular to the second transverseaxis and the third transverse axis is substantially perpendicular to thefourth transverse axis; wherein the first transverse axis issubstantially perpendicular to the third transverse axis and the secondtransverse axis is substantially perpendicular to the fourth transverseaxis; wherein each of the support frame and the centering support frameare discrete structures interconnected at two or more points; andwherein the opposing bends at the first and second ends of the supportframe are the only bends in the first and second ends of the supportframe.
 2. The valve prosthesis of claim 1, wherein the support frame andthe centering support frame are formed from a cannula.
 3. The valveprosthesis of claim 2, wherein the cannula comprises metal.
 4. The valveprosthesis of claim 3, wherein the metal comprises stainless steel. 5.The valve prosthesis of claim 3, wherein the metal comprises nitinol. 6.The valve prosthesis of claim 1, wherein the support frame and thecentering support frame are formed from wire.
 7. The valve prosthesis ofclaim 6, wherein the wire comprises rounded wire.
 8. The valveprosthesis of claim 6, wherein the wire has a cross-sectional shapeselected from the group consisting of oval-shaped, delta-shaped, andD-shaped.
 9. The valve prosthesis of claim 6, wherein the wire comprisesflat wire.
 10. The valve prosthesis of claim 1, wherein the supportframe and the centering support frame are interconnected by a shortstrut.
 11. The valve prosthesis of claim 1, wherein the two or moreleaflets comprise a biomaterial.
 12. The valve prosthesis of claim 11,wherein the two or more leaflets comprise a remodellable material. 13.The valve prosthesis of claim 11, wherein the two or more leafletscomprise an extracellular matrix material.
 14. The valve prosthesis ofclaim 13, wherein the extracellular matrix material is selected from thegroup consisting of small intestine submucosa, pericardium, stomachsubmucosa, liver basement membrane, urinary bladder submucosa, tissuemucosa, and dura mater.
 15. The valve prosthesis of claim 13, whereinthe extracellular matrix material comprises small intestine submucosa.16. The valve prosthesis of claim 11, wherein the two or more leafletscomprise elastin or elastin Like Polypetides (ELPs).
 17. The valveprosthesis of claim 11, wherein the two or more leaflets compriseharvested native valve tissue.
 18. The valve prosthesis of claim 1,wherein the two or more leaflets comprise a synthetic material.
 19. Thevalve prosthesis of claim 18, wherein the synthetic material comprisesDACRON or expanded polytetrafluoroethylene (ePTFE).
 20. The valveprosthesis of claim 1, wherein the two or more leaflets comprise twoleaflets.
 21. The valve prosthesis of claim 1, the first and secondouter edges of the two or more leaflets are wrapped around obliquelyopposite frame elements.